First biome is all about getting gems. Do this by just ignoring everything and collecting gems, or by only hunting big multi point monsters. Single hit point monsters are at best a distraction and annoyance, at worst a thorn-stealing nuisance. I actually have a hunch the optimal strategy is to bypass all seed plots and just rush the middle random room, and if you don't get something useful, to restart. Ideally, you'd get something with a positive return on investment that is an attack, and then work your way down the level, kill all the mobs and collect their gems, and work your way back up. Not difficult, but just too boring to seriously consider.

Second biome is also all about getting gems. Ideally you have some way of farming effectively from spawners, like red hot rock, or bomb, or flyseed, or star, or something. Farm the spawners. Ideally you also have either digseed or gardener by this point. Then you're laughing.

Third biome is about survival. Best tools here are digseed/gardener and star, or just reflect seed. Either of those combos will cause you to breeze through this biome with tons of extra gems and not a lot of fear of lost hearts. Reflect seed alone could carry you through this one.

By the fourth biome, you should be well stocked and as long as you have star/reflect and bomb/homing-shot, you'll breeze by.

As for the boss, what a mess. I'm not even sure. Just do what you can, you ideally have a basically limitless supply of gems by this point, and a huge arsenal of seeds. Having no way to effectively crowd control like bomb or homing shot, or something like star or cloak to avoid crowds, and you're probably done.

My preferred rollout is probably homing shot first because it is so useful at every stage of the game. Then reflect seed, or star, I'm really not sure which is better in the long game. Probably star, if I can only have one. Then, I really want digseed or gardener. I think if I get those, I don't care what else I get.

(totally right, optimal strat is rushing the first random room, working your way back, and then up)

First biome thomp. Best starting seed, hands down.

awesome, this is super interesting. gonna sticky this in hopes more folks share their strategies.

I 100% agree first biome is for accumulating that cash money. I try to avoid dropping a checkpoint seed at all, I'm that greedy.

Second biome is where I try to build up half cash, half hearts. I try to have at least six hearts and twenty crystals by the end of the third biome.

I try to have at least one seed that does up-close combat well (knight seed, hot rolling rock) and one that handles projectiles well (reflect, shield). Possibly a third seed for dealing with the third biome's projectile hell (slow motion, invisibility). I'm keen on the star seed now too, as that one is super useful in the fourth biome and the final battle. Really lets you focus on moving upward without worrying about all the other chaos happening around you, and with enough time put into the game, you can make a ton of progress in that short star seed window.

Hole filler is huge in the fourth biome. It'd probably make the final battle easier, too, though I used a star seed to rush through that.

I think generally my strategy depends on what I'm given, and I try to buy what I didn't get for free.

So far I try to use the bank in the first camp. I'm still avoiding minigames for health reasons but I'll get back to them soon enough. Extra crystals would be great.

But at this point I feel like I'm mostly relying on luck to give me good seeds for free. The enemies and projectiles are tricky, but I love the increased hole density, since it's difficult but rarely feels cheap (the way being overwhelmed by too many enemies or bullets can feel cheap).

But to summarize my priorities are, in this order:

1. Get money
2. Get hearts
3. Get the right offensive seeds (knight, hot rock)
4. Get the right defensive seeds (shield, reflect, star, hole filler), ideally before the third biome

In terms of how to maximize first biome strats for maximizing what you have going into the second biome, here's my suggestions:

Run to the first random room, trying to touch nothing but crystals. Avoid all plots and enemies. If you don't get Horizontal Thorns, Vertical Thorns, Star, Thwomp, or Homing Seed, find the nearest spikes to kill yourself. Run to the random room again. Do this until you end up with one of those. Ideally Thwomp, because it is the seed I find useful most evenly across the entire game, but Star can be the difference between a good boss attempt and a flail, so play according to taste.

Work your way back down the first biome, trying to minimize the number of plots you use to kill the maximum number of enemies. That's why Thomp is the best at this. Use all other seedplots for hearts. Work your way up the first biome from the bottom with this method.

Ideally in the first camp, find a magnet aura. Do the challenge room, which with magnet aura and your run through the first biome should mean you have 30-50 crystals, and ideally 5+ hearts (assuming you aren't a derp like me and let your good pal thwompy hit you). Put some crystals in the bank. Buy every seed in the store. Not because you actually want them (although if they are good drops, then yay!) but to minimize the possibility of them showing up later in the game when you need something else.