The Depths is the third environment the player encounters. It takes the shape of a grayish stone cave, littered with bones.
In addition to pits and spikes, this environment features Stone Grimaces that will shoot at the player until all enemies on the room are defeated. These statues can be harmed by technology but not able to be moved.
Also, Keystones are present: these blocks can only be removed by touching them and spending one key. They typically block off access to a chest or slot machine and when removed may randomly drop a free pickup.
- Boom Fly
- Knight (Upgraded versions also appear, but are rare)
- Leech (Rare, upgraded version is even rarer)
- Mr. Maw
Boss monsters found in normal rooms
- Blastocyst (Embyro forms or very rarely, smallest shelled versions)
- Fistula (Multiple small or medium pieces in the same room)
- Larry Jr.
- Monstro II
- Mom (Always encountered in Depths II/XL)
- War (once unlocked)
- Gish (once unlocked)
- The Headless Horseman (once unlocked)