| Achievement | How to unlock
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- A New Career in a New Town
| - Get the true ending as Lydia.
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| - Get the true ending as Cordelia.
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| - Beat the game as Cordelia.
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| - Loop twice in a single run.
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| - Leap off the balcony and loop your run.
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| - Collect 15+ items in a single run.
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| - Unlock the B costume for every character.
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| - Clear the game on 'Painful' difficulty.
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| - Clear the game on 'X Must Die' difficulty.
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| - Clear the game on 'Nightmare' difficulty.
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| - Get the true ending as Luis.
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| - Carry over $1,000 at once.
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| - Carry over $3,000 at once.
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| - Carry over $2,000 at once.
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| - Get the true ending as Jules.
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| - As Fuji, kill a boss in under thirty seconds.
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| - Get the true ending as Mumba.
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| - Collect 25+ items in a single run.
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| - Kill a Moth using a melee weapon as it's coming at you.
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| - Purchase Cordelia's entire stock on the first floor.
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| - Collect 35+ items in a single run.
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| - Assemble all four parts of the Silver Key.
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| - Purchase a shop's entire stock as Cordelia.
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| - Kill 6+ enemies with less than a second gap between each kill.
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| - Break ten golden pots in a single run.
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| - Get a Crusher in the Laboratory to land on Chunks.
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| - Obtain a Mumba Launcher as Mumba.
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| - Get 10+ reward items in a single run as Lydia.
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| - Clear a run without picking up, firing, or scrapping a single weapon besides your Shotgun or Rocket Launcher as Jules.
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- Orange County Lumber Truck
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| - As Digby, get a 20+ kill combo.
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| - RUNRUNRUNRUNRUNRUNRUNRUNRUN.
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| - Get the true ending as Jeff.
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| - Max out all your stats with Dr. Cordelia.
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| - Destroy 5+ weapons in a single run.
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| - Visit ten secret rooms in a single run.
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| - Destroy a full ammo Golden Gun as Luis.
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| - Get the true ending as Fuji.
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| - Press all three buttons in the Exit Realm within five minutes.
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| - Complete a run in twenty minutes or less.
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| - Clear a challenge room in fifteen seconds or less.
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| - Unlock Mumba's B costume.
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| - Unlock Lydia's B costume.
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| - Unlock Digby's B costume.
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| - Unlock every character in the game.
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| - Unlock Jules's B costume.
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| - Unlock Cordelia's B costume.
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| - Clear the Foresaken Crypt.
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| - As Jeff, clear a run without any items.
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| - Get the true ending as Digby.
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| - Complete a run without ever visiting a shopkeeper.
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| - Complete a run without taking a single hit.
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