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Now whenever you find an Angel room, you can bomb the angel statue inside. This will trigger a boss battle, which upon beating them will drop a key piece. You then have to find a second angel room and repeat the process to get the other key piece. Then, once you reach either the Chest or the Dark Room, the key will be consumed to open Mega Satan's Door. Once you go in, you can't come out, so it's best to clear the floor first to get whatever achievements you need and power up from the items before going to fight MS.
Note, his door is not a permanent unlock, you have to complete the key every time you want to fight him. There are two other alternate ways in, though. One is using Dad's Key on the door (this item unlocks after completing the key to Mega Satan's door for the first time), and the other is using the Get Out of Jail Free card, which is the reward for Challenge #22: Speed.