- Unlike in the first title where you could fully heal your three party members to full hp whenever you'd like, you can only heal them once the circular "medkit gauge" near your MC's hp bar has at least one stock in, though thankfully you can still "revive" downed party members without a medkit stock, just at reduced hp than if you were carrying a medkit stock.

- There aren't any "passive skills" in the skill shop (this is accessable after completing the first mandatory Act 1 mission of SotDSH that you start on, for those of you fresh to the SotDSH scene either after completing the first chapter or not) so even, say, you purchase a skill and think it'll go into effect, it won't. You need to manually place it into one of your skill slots, and you only begin with a few unlocked, but you unlock a few more slots later as you level up further, the max level being lvl 30, though you can still accrue points after maxing your level of course.

- The R18 patch (not to be confused with the "demosaic patch") actually makes it tougher to defend your downed party members, whereas the non-R18 variation has your downed party members only non-lethally "attacked" by common infected and so forth instead, making them excellent aggro-bait, but for those, like me, who prefer the "unlocked" experience, your party members will be in danger of being sexed-up by both common infected and special infected with the R18 patch applied, so be wary of that.

- Whenever you're healing/reviving a party member there's a fairly-rough chance of triggering an annoying "special infected spawn" so also be wary of that annoyance whenever healing or reviving your party members and utilize closed indoor infrastructure as much as possible to prevent them from causing too much havoc as you're reviving/healing your party members.

- When you first install SotDSH, unlike the first title before it which has full R34 content unlocked from the start (though it still includes the mosaics, but you can remove those with the alternative method patch via the "demosaic guide" for it), you need to manually apply the R18 patch to unlock R34 content in SotDSH, otherwise it sticks with its non-R34 variant. You can easily find it via Googling "Seed of the Dead Sweet Home R18 Patch" (without the "s help narrow it down to its EJ site from what I can see) and acquire it from the ErogeJapan site.

- The NTR events (available only in the R18 variation of SotDSH obviously) are exactly as you can imagine them from their namesake alone. According to the "Item Guide" creator it starts out without the MC but later ends up with "sharing" h-scene events at the ending parts of the NTR quest branch. If you're not into that kind of NTR crap (I too am heavily opposed to it, in the "maledom" regard anyways) then just select the "hide" option on one of them and the rest will disappear, though be warned that one can't begin them after choosing this, so be absolutely sure of this, dunno how to undo the "hiding", though I doubt it'd be too hard to figure out.. (the resultant items such as the Tattoo "permanent" item for instance can still be bought in the item shop regardless afterwards, so no worries about those missing forever)

- During the Bath mini-game, after the first stage, instead of using the water nozzle to spray all over the girl's body, instead focus on the small "pinkish-purple spots" that appear until each are gone. This had me very irritated until i finally figured this annoyance out after two annoying failures on the second stage. ><

- During the Act 4 mission, while you can sprint-jump across the rocks on the right-most side of the lake to reach the inner small island with the statue along with a potential item/weapon, I tried jumping back over after combing over every way I could find and wasn't able to sprint-jump back across the rock I used to get around the lake, as the lake can't be crossed by wading through it unfortunately, thus forcing me to quit (retire) the mission, so bear that in mind. I'm guessing that it "might" ("might" being the key term) unblock the way into it naturally later when you access the interactable iron gate that leads to the academy's interior, though i'm not sure. Regardless though, something to keep in mind.

- You can only apply one mission-long enhancement (Such as the "Stab-Proof Vest", "Magazine Expansion" and "Reinforced Bullets" and so forth. I tried to apply all three of the above for each girl I started the mission with in preparation for the "boss" in the Act 5 mission, but sadly only the "Reinforced Bullets" stuck, thus wasting my hard-earned points, gah... DX) item for each girl you bring on your next mission, so bear that in mind to avoid wasting valuable points like I stupidly did. ><

- Tintans (the large mutants with bright, white eyes that charge at you in a superhuman-like fashion with energy-infused auras and so forth) are usually only vulnerable in the "head" area (though I recall being able to damage it with the SPAS 12-like shotgun on its other areas, but it may have to do with its "armor" stripped off via grenades or some such since I dunno how this happened otherwise) in this story (unlike in the first story where they were vulnerable all over), at least on "Very Hard" difficulty as i'm unsure if they're vulnerable all over on the other difficulties, but as I prefer the challenge, on "Very Hard" difficulty at least i've noticed that all other areas shot at are like firing at a steel wall, so i'm "guessing" that it's only vulnerable at its head, though i'll need others to confirm if its "armor" can be stripped off somehow, likely via grenades. All-in-all, focus fire around the head area so that it affects the annoyingly hard-to-kill Tintan f***er more.

- The Act 5 boss is thankfully less hard than fighting a Tintan since it's vulnerable on all areas of its body as the only real gimmicks it has are its teleport-spam, entrap attacks toward the girls when it throws its scythe blade at them and they don't dodge (you have to shoot at the worms entrapping them, I used the grenade launcher and it worked wonderfully) and calls a few common infected to aid it (though thankfully there's no special infected that arrive during the battle) and that it uses a scythe blade spin once it gets a sizable chunk of its hp bar depleted and scythe charge attack in which it teleports to a random spot near you and rushes in a straight line forward. Other than that, it's easily handled as long as you brought the CM2000 anti-materiel sniper rifle along with you with full ammo reserves for both the grenade launcher and the anti-materiel sniper rifle. (The SKS is a tame alternative to the CM2000 in case you have the rotten luck for it to not spawn at the beginning of the mission like it normally does as it does seem to have an annoying rng-based chance of not spawning at the beginning after all.)

- If the girl you're seeking to heal keeps on running away from you then just stay where you are and eventually she'll stop running from you and you can more easily catch up and heal her then, dunno why this happens but it's absolutely infuriating whenever it happens.

- Prepare in advance for the forced solo section in the Act 7 mission at the end of it by making sure to have the Steel Body 3, Ammo in Socks 3 and Main Reload Speed 3 skills active at the very least as you'll need to defeat 95 types of various foes before the timer gets depleted.

I equip the Recovery Rate Increase 3, Remission 3 and Full of Vitality skills alongside the previously mentioned skills so that I can keep the girls and my hp up as needed so that they won't be easily downed during the trek to the mansion and its underground ultimate destination. I also highly recommend bringing the CM2000 anti-materiel sniper rifle (or the Pulse Rifle if you see it spawn near the event-triggering gate as it REALLY rips through common and special infected alike when used properly, though be warned that it has a short "warm up" before it blasts full auto, meaning you'll likely be better off with CM2000's more reliable raw AP firepower) and the grenade launcher (don't use it too much on special infected though, use it mainly on the annoying common infected masses since you only have 60 spare rounds so try to make each shot count) with full ammo reserves for both, be wary of the female special infected as they can restrain you. (In the R18 variation at least, dunno about the non-R18 version) Apparently her restrain attack occurs when she does her high jump attack, so be especially wary of that annoying move, I CANNOT overstate this enough as it leaves you WIDE OPEN for the other teeming foes to openly wail upon you) and thus waste both your precious valuable time and temporarily-unreplenishable hp to deal with the other foes as the timer ticks down and know that since the girls are trapped in this section, you won't be able to heal so take that into account as well. With enough luck, you'll be able to get through this extremely annoying part. (don't forget that there's a unique "present robot" type enemy that strolls in as the battle progresses that drops the unique "Lingerie" costume, get it if you can as the robot itself is harmless [if you want the costume for the other four {three if you lack the "Charm Song" dlc that gets unlocked after the main non-dlc story is concluded} girls then, unfortunately, you'll need to endure doing this annoying part more than once, but thankfully you can simply skip to the mansion's entrance hall via the "relay/checkpoint" option upon revisiting the Act 7 mission], it even tries to flee from you so that your acquisition of the costume is harder whilst fending off the other enemies)

- The final boss of Act 8 has none of Act 5's boss' annoying "teleport spam" crap it had before and is basically a different breed of the good ol' "El Gigante" boss from RE4 (the original, not the BS-remake obviously), just that it mainly uses shockwave stomps/jumps and it gets a rushing charge attack as its hp gets lower and lower. Also, it eventually absorbs your girl party members one by one at a steady pace, though thankfully their health doesn't deplete over time and simply remains stuck into the boss so, unlike the EXTREMELY ANNOYING "timer" section in the Act 7 mission end, you can take your time dislodging them by shooting the area around each girl, dunno if this happens in the non-R18 version though but if it doesn't then you'll have an easier time taking down the final boss of the vanilla SotDSH chapter since the boss is a relaxing vacation compared to the EXTREMELY ANNOYING "five minute timer" section on Act 7, dead serious here... DX
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(from this point, the rest of the tips involve the "Charm Song" dlc chapter, so simply ignore from this line onward for those who don't currently have it/have no intention of getting it sometime in the future)

- The concluding event on Act 9 involves a scenario similar to RE4's Cabin holdout (the one at night with Luis, just to clarify), though unfortunately, unlike RE4's Cabin holdout section, you have a MUCH shabbier "cabin" and the enemies eventually start adding on, so basically you need to hold out and eliminate as many enemies as possible (and if you have the R18 patch installed, make sure to not let your girl's post-down meter fill completely obviously) until you hear the same "screech" you heard before in the cutscene before it, this usually signifies the mission's end fortunately. In all honestly, I dunno what skills, other than Remission 3, Steel Body 3, Recovery Rate Increase 3 and Main Reload Speed 3 to bring, since there's various kinds of skills that can help in regards to this section. (At least it's doesn't have an annoying "timer" like the final bit in the Act 7 mission did at least.) Ammo in Socks 3 isn't much of a priority in this mission now that I think of it, especially since you're given multiple ammo crates in which to refill your ammo at in the cabin, thus ammo is generally a non-issue in this mission most of the time, the only real issue are, as usual, the ever-annoying Tintans and female special infected who, once again, LOVE to restrain you after successfully hitting you with their high jump attack. That and the ever-growing masses of annoying common infected that have a very high chance of surrounding you during this part. As such, judging from this part in this video here, it seems that the Molotov variation of the grenade works absolute WONDERS during this part since, unlike in most other titles, it seems the flames from molotovs don't hurt either the MC or the girls and as such it makes for an EXCELLENT area-denial weapon for as long as the flames rage on against the common infected. This being the case. It might be worthwhile to have Molotov Cocktail and Gren Increase 3 skills active alongside the previously-mentioned four skills during the Act 9 mission to help immensely during the Cabin holdout part against the common infected since I recall that there's two grenades around the Cabin, meaning you can restock six grenades with the Gren Increase 3 skill active. This combined with the Molotov variation of the grenade means you'll have a LOT more breathing room against the common infected, so that by itself will be a tremendous relief. It also wouldn't hurt to equip the three girls you choose to travel with with Stab-Proof Vests so that they'll have higher hp and can tank more attacks before being downed.

- In Act 10, be wary that, the straightaway after passing the CM2000 rifle on the bench in the amusement park near the ferris wheel, contains not one, but two Tintans, so be ready to use that anti-materiel rifle (or the pulse rifle if the CM2000 doesn't spawn on said bench) on them after backpedalling a bit and, hopefully, they'll get "stuck" on the fallen, fixed props (I managed to have one of them be "stuck" on them, thereby getting rid of the other a LOT more easier) resembling large red pipes. (After doing a second run of the Act 10 mission i've noticed that the CM2000 got replaced by a stock N90 LMG, so apparently it isn't always the CM2000 that spawns there.) Before that, a pulse rifle can be found on the rightmost path after getting through the short bamboo maze with the scripted flamethrower spot, combining this with the CM2000 will make getting through most situations in this mission a lot easier when utilizing both to their best potential, especially against the single Tintan that is scripted to appear when you're about to enter the amusement park entrance or hiking up the hill before taking the aforementioned rightmost path. Also, the boss in Act 10 pretty much shares the Act 5 boss' Scythe blade moveset, only that it hits like a tank, but fortunately lacks the Act 5 boss' teleport spam ability and also moves slowly like a tank to compensate, be careful against it though since it can ero one of the nearby girls, but thankfully they can be dislodged with a shot to the boss. And like the Act 5 boss, there's scripted common infected but thankfully also like the Act 5 boss there's no special infected with them. All-in-all it's not as bad as Act 9's cabin holdout, that's for sure.

- Near the end of the Act 12 mission, after using the roofside (not the first one) zip line, after traversing a bit past the area with the ammo box, you'll encounter an annoying acid-like substance that will start flooding the building akin to the "Toxic Tower" level from "Donkey Kong Country 2". Thankfully though, this variation isn't an insta-kill substance, but it does slow you down whilst escaping to the upper floors to escape it and only sheds 1 hp every few seconds. Still though, speeding straight to the "goal area" helps immensely during this part of the mission, just be wary of those exceedingly-annoying female special infected whilst making your way to the goal area upstairs.

- For the final Act 13 mission, be sure to save all ammo for invaluable types of weapons such as the CM2000, LAR lever-rifle and so forth, since you'll be spamming your Nikita rocket (it takes the place for your heal command during the first and second phases) more often than your own weapons, as there's no ammo boxes in this stage, so be sure to save all ammo for your invaluable weapons for the final third phase of the boss fight, you'll thank me later, trust me. DX
However, feel free to use ammo for junk weapons such as SKS, the pump-action shotgun and SMG during the first and second phases though of course, as those aren't as invaluable as the other listed above examples
For this mission you'll want to equip the Recovery Rate Increase 3, Full of Vitality, Steel Body 3, Molotov Cocktail, Ammo in Socks 3 and Gren Increase 3 skills for this mission, as there's a "slow down" effect whilst healing during this mission for some reason, even during the final third phase of the boss, so you can utilize that as well. The mini-spiders have a chance to drop either grenades or vit-can, so those will be your only real "resupply" source during this mission and thankfully the mini-spiders in this mission aren't as tanky as they were in the previous Act 12 mission, so that by itself is a big relief obviously since, for the first and second phases of the boss fight, it's pretty much a spider-thon. On the third and final phase, it's best to have either the CM2000/LAR and Pulse Rifle on hand, as the girls will periodically get entrapped by a circular wheel move that can only be undone by the MC shooting them off the girls, and when the boss has around 75% of its hp shaved off, it then periodically entraps ALL girls from time to time (though some are exempt if they're in the middle of the heal anim though) at that point. At that point you'll see just why I said to conserve all non-junk ammo for this phase of the boss fight.