If you're referring to Act 1's boss, it's all based on how your deck is built based on synergies, if you don't have the correct synergies, you're bound to lose

Usually the starting hand is literally luck based, but if have a large deck full of bones or high cost blood cards, you're not going to have an easy win or even more likely bound to lose

Try to look for cards that compliment each other, of course, the more you lose the easier Act 1 will get, especially when it comes to creating custom/death cards

Note: If you have high blood costs in your deck, try to get a Black Goat in your run, alternatively, if you have a lot of bones in your deck, you could even, Spoiled feature incoming use the Black Goat & use it to sacrifice it to the Bone Lord where it would normally give you a bone offering you'll get the upgraded version that starts every round with 8 Bones

If you can save items prior to the final boss it'll help if you're usually struggling, aim for that goal

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Good Luck & Have Fun

i don't think i did any savescumming in my vanilla run since i knew this was a rouge-lite so dying was a necessary part of the experience and i wasn't in a hurry to finish the game or anything, but kaycee's mod, while hunting the harder achievements? yeah.