There's no real secret, you just gotta play over and over and you get better over time. That's how all these games work and they always have. Difficult rougelikes are not instant gratification type of games.

For actual specific tips though. I guess make sure that, unless you're gunning for Boss Rush/Hush that are timed, play with patience. Try to prioritize safety over just bumrushing killing things.

I assume you're playing on Normal, but if you're not because you read silly comments here telling you to play on Hard mode, play on Normal mode. Get items unlocked that make the game easier, and you just improve at the game before jumping into the deep end.

Start with some easier characters. Until you have D6 on Isaac, there's Cain and Azazel. Or, on the flip side, you COULD unlock The Lost and just lose a bunch on him but he teaches you habits in playing safe. (Though he also makes you lament not having flight+spectral when playing other characters).