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Challanges dont get you to mega satan, dont know how much you whant me to spoil but keep kill moms heart and you will go deeper :).
Play because its fun and you will get better. Dont think there is a secret tips that makes you win in isaac you just need to play and learn. The wiki is good if you whant to look somthing up.
As an expert in twin stick games - I can tell you that even if I drop a game of the genre for a very long time, I can jump back into it ALMOST as if I never stopped playing it.
The trick is to recognize AI behavior, mixed with gained knowledge about items, combinations and mechanics.
Execute your input by recognizing repeating patterns and situations, rather than thinking on your feet (although it's also important).
If you're REALLY struggling, watching Youtubers like Northern Lion play the game can really help. I learned about techniques I'd never thought of that I now fully incorporate into my play.
Try to avoid playing characters with trash unlocks or achivements with them that unlock trash. Then once you've unlocked pretty much everything good, then go for 100 percent.