How to Advance
First start playing with Isaac, dying is ok and experience makes the expert, as many items as possible in a run, start advancing to new floors, it is hard at the start at the first time, strategy is to start getting items that will make your game easier, first unlock that will make your game so very incredible easy is getting Azazel, this character has a short brimstone which is so useful to start advancing in floors, Azazel is unlocked when getting 3 devils deals in a single run, i recommend that when finding a triple devil deal, take all, no matter if you die, you will unlock Azazel, or you could also be playing and getting a lot of devil deals, when getting Azazel you will be able to advance a lot, next achievement is to get the epilogue, which is obtained when killing mom for first time, also, when killing her you will unlock the womb/utero.
Start getting all character and kill mom’s heart with all of them, when doing this, you will start getting a lot of completion marks; for example, get Cain (unlocked by 55 pennies in a single run), this character is really easy, it has high speed and good damage, or with Magdalene, killing mom’s heart will give you new items, but the objective is getting it lives! (when killing mom’s heart 11 times) this will also give you the gateway into the Sheol and the cathedral, I highly recommend start going to cathedral, since in the Sheol you will find a lot of hard enemies and traps, cathedral’s final boss is Isaac, hard first time, recommend starting with all characters to get a lot of unlocks, the only hard attack Isaac has is the lights from sky (sky fractures) which you will need to learn, or you can go to Sheol.
Sheol has amazing unlocks, mom’s knife is the item that everybody likes, high tick damage and it is easy to handle, sheol can be beaten easily if you know all enemies attacks, final boss is satan, which will spawn the fallen at first and then will appear attacks aren’t that hard.
Kill 5 times Satan or Isaac to unlock the negative and polaroid, will let you to go to dark room and the chest, definitely go to the chest first, because the dark room is so very hard, it has the hardest bosses in the games and the lamb which is highly hard, well that is the guide, thanks for reading, comment if i missed something and tell me what is it, i will make a second part if this has support, bye-bye and good luck!