The Binding of Isaac: Repentance offers a vast array of items, many of which interact with each other in complex and often hilarious ways. The game is an example of a "roguelike" game, meaning that each playthrough is different, with levels randomly generated, and upon death, progress is reset. This genre appeals to players looking for a challenge and a high replay value.

: Over 30 playable characters, including 19 new additions like Bethany and Jacob & Esau, plus unique "Tainted" versions for every character.

: Installing mods on a cracked version is more complex since the Steam Workshop is not directly accessible. Guides on The Modding of Isaac suggest alternative manual installation methods.