Challenges
| Name | Character | Starting items | Disabled rooms | Curse filters | Additional notes | End goal | Unlock condition | Reward |
|---|---|---|---|---|---|---|---|---|
| 1. [FF] Frog Mode | Slippy | - | - | - | - | Mom's Heart | - | Slippy's Guts, Slippy's Heart, Golden Frog Head, Frog Puppet, Tattered Frog Puppet |
| 2. [FF] Isaac Rebuilt |  Tainted Magdalene | The Belt
Birthright 4.5 Volt Sanguine Hook | - | Killing enemies with Sanguine Hook makes them drop  Half Hearts which disappear after a short while. | Mom | - | Deimos | |
| 3. [FF] Tower Offense | Golem | Brown Nugget
Boom! 6 random Grimlin trinkets (4 smelter, 2 golden) | - | The 6 Grimlin trinkets are rerolled in every room.
Golem is unable to access the Subway. | Mom | - | Lawn Darts | |
| 4. [FF] Handle With Care | China No HP. | - | - | - | - | Mom | - | Heartache, Cursed Urn, Shattered Cursed Urn |
| 5. [FF] The Gauntlet | Isaac | - | - | - | Isaac starts with 3¢ and no bombs.
The challenge takes place in a single custom-made stage whose goal is to defeat every single boss and mini-boss added in Fiend Folio, with the exception of Hermit. The challenge consists of multiple sections with a unique boss, each featuring a hub area that offers items and consumables for purchase. Stage paths are blocked with Colored Locks, the only way to unlock them being by defeating bosses, which each drop a Colored Puzzle Key corresponding to these locks, in addition to 7  Pennies.
Entering a section causes the previous section's door to be permanently sealed. | Gravedigger | - | Community Achievement |
| 6. [FF] Brick By Brick | Golem | Brick Rock (2x; one is golden) | - | Brick Rocks re-appear on impact, and are slowly attracted to Golem.
The golden one attracts slower than the other one. | Mom | - | Brick Seperator | |
| 7. [FF] Dad's Home+ | Isaac | - | - | - | Every encountered enemy and boss respawns in a random location in other rooms, even if they have been cleared.
This also includes other entities such as TNT and Shopkeepers. | Stage 2 | - | Green House |
| 8. [FF] Dirty Bubble Challenge | Isaac | - | - | - | Every enemy projectile is replaced with a Bubble of a random size.
Some flaming or explosive projectiles are replaced with Explosive Bubbles. Homing projectiles are replaced with Fly Bubbles. | Mom's Heart | - | Petrified Gel |
| 9. [FF] The Real Jon | Isaac | - | - | - | A unique Elite Jon enemy constantly follows Isaac throughout the run.
This enemy cannot be damaged or killed unless Chaos Card, Euthanasia, or similar effects are used, in which case it will reappear in the next room. | Mom's Heart | - | Spare Ribs |
| 10. [FF] Hands On | Isaac | Transcendence
Pointy Rib Grabber (x3) | - | Grabbers are mirrored across from Isaac in all 4 movement directions. | Mom | - | Grabber's Enemy | |
| 11. [FFBonus!] Mr. Hands | Isaac | Grabber's Enemy (golden)
Forgotten Lullaby (gulped) Baby-Bender (gulped) | - | Fast homing hands fly across the screen in every room, grabbing anything in their path.
Every time Isaac takes damage, gulps another copy of Grabber's Enemy, increasing the number and frequency of the hands. | Mom's Heart | - | - |