
The majority of items are unlocked by completing specific in-game milestones, such as killing a certain number of enemies with a damage type or achieving challenging run goals.
| Item | How to Unlock | Effect |
| Anvil | Complete 3 challenges | Weapon upgrades can now have +2 stats. |
| Backpack | Unlocked by default | +1 Projectile Count for all Weapons. |
| Battery | Upgrade the Cooldown Tome to Level 5 | +8% Attack Speed. |
| Beacon | Unlocked by default | Charging a Charge Shrine creates a healing zone and spawns +2 extra Shrines in future stages. |
| Beefy Ring | Unlocked by default | Adds +20% Damage per 100 Max HP. |
| Beer | Unlocked by default | Adds +20% Damage at the cost of -5% Max HP. |
| Big Bonk | Unlocked by default | 2% chance to BONK an enemy, dealing 20x damage. |
| Bloody Cleaver | Reach Level 50 as Vlad | Lifesteal now activates Bloodmark stacks. Also adds 50% chance to apply Bloodmark. |
| Bob (Dead) | Survive the Final Swarm for 2 minutes | For every 14 units moved, summon Bob (dead). |
| Borgar | Unlocked by default | Has +2% chance to spawn Borgar on kill, healing you. |
| Boss Buster | Defeat a Stage Boss in under 30 seconds | Gives +15% more damage to Elites and Bosses. |
| Brass Knuckles | Kill 5,000 enemies with the Sword | Gives +20% damage to nearby enemies. |
| Cactus | Kill 100 cactus enemies with Thorns damage | Shoots spikes when taking damage, scales with Thorns. |
| Campfire | Unlocked by default | Standing still heals you. |
| Chonkplate | Reach 500 Max HP | Grants +20% Lifesteal and allows overheal up to 75% of Max HP. |
| Clover | Unlocked by default | Adds +7.5% Luck. |
| Coward’s Cloak | Unlocked by default | Boosts Move Speed when hit; +5% base Move Speed. |
| Credit Card (Green) | Unlocked by default | Adds +2% Luck when opening a chest. |
| Credit Card (Red) | Unlocked by default | Adds +2.5% Damage when opening a chest. |
| Cursed Doll | Die 10 times | Curse enemies, dealing 30% of their Max HP as damage per second. |
| Cursed Grabbies | Get the Cursed Tome to Level 10 | +10% Difficulty, 0.8x Max HP, 5% chance to cast curse on hit. |
| Demonic Blade | Heal for 350 HP using Lifesteal | Critical hits have a 25% chance to heal you. |
| Demonic Blood | Increase your Max HP with Blood Magic 400 times | Gives you +9 Max HP, bonus Armor and Thorns. |
| Demonic Soul | Reach Level 30 as Calcium | Gives +0.1% Damage per kill (up to 100%). |
| Dragonfire | Kill 4,000 enemies with fire damage | Has a 15% chance on hit to summon dragonfire that burns enemies. |
| Eagle Claw | Kill 10,000 enemies as Birdo | 66% Damage vs airborne enemies, 8% chance to launch them into the air. |
| Echo Shard | Upgrade the XP Tome to Level 8 | Has +12% chance to spawn a bonus XP Shard on kill. |
| Electric Plug | Unlocked by default | On taking damage, send out an electric shock. |
| Energy Core | Defeat a Final Boss 2 times | Gives a cooldown reduction and energy regen. |
| Feathers | Unlocked by default | Lets you jump higher and further. |
| Forbidden Juice | Crit 100 times in a run | Gives +10% Crit Chance. |
| Gamer Goggles | Defeat a Stage Boss with less than 10% HP | Increased damage the lower your HP. |
| Gas Mask | Kill 5,000 enemies using Amog | Gain Armor and Lifesteal for each poisoned enemy. |
| Ghost | Survive the Final Swarm for 60 seconds | Summons ghosts using an interactable. |
| Giant Fork | Unlocked by default | Crits can become Megacrits. |
| Golden Glove | Unlocked by default | Earn +15% more gold from kills. |
| Golden Shield | Unlocked by default | Gain gold when taking damage. |
| Golden Sneakers | Break 150 pots | Earn money by moving. |
| Grandma’s Secret Tonic | Kill 3,000 enemies with the Sniper Rifle | Crits have a 50% chance to exploding, dealing 50% damage. |
| Gym Sauce | Unlocked by default | +10% flat Damage. |
| Holy Book | Kill the first Stage Boss without taking damage | +100 Max HP, +50 HP Regen, healing radiates damaging energy. |
| Ice Cube | Unlocked by default | 20% chance to inflict ice damage; ice can now freeze. |
| Ice Crystal | Get 50 kills with Frostwalker | 7.5% freeze chance; executes enemies at threshold HP. |
| Idle Juice | Kill 500 enemies while standing still | +100% Damage cap while stationary. |
| Joe’s Dagger | Kill 10,000 enemies using the Dexecutioner | 1% chance to Execute. Each Execute adds +1% Damage. |
| Kevin | Get 3 Leeching Crystals in one run | 25% chance to punch you on hit (cannot kill you). |
| Key | Purchase 25 chests | 10% chance for chests to open for free. |
| Leeching Crystal | Upgrade the Regen Tome to Level 8 | +50% Max HP at the cost of -50% HP Regen. |
| Lightning Orb | Kill 3,000 enemies with lightning damage | 25% chance to summon lightning on hit; can stun. |
| Medkit | Unlocked by default | +45 HP Regen. |
| Mirror | Unlocked by default | Reflects all incoming damage and grants brief invulnerability. |
| Moldy Cheese | Unlocked by default | +40% poison chance on hit. |
| Moldy Gloves | Use a Microwave to duplicate Moldy Cheese 3x | Creates a moldy poison cloud on hit. |
| Oats | Unlocked by default | +25 Max HP. |
| Overpowered Lamp | Unlocked by default | +1 proc chance on hit effects. |
| Phantom Shroud | Unlocked by default | After evading, next hit deals 2x Damage; boosts Attack Speed & Move Speed briefly. |
| Power Gloves | Unlocked by default | 8% chance to create a giant blast on hit. |
| Quin’s Mask | Defeat a Stage Boss as Athena with Aegis | Thorns damage has a 50% chance to explode. |
| Scarf | Unlocked by default | +33% Damage while airborne. |
| Shattered Knowledge | Upgrade Attraction Tome to Level 8 | XP Shards slice through enemies on travel. |
| Skuleg | Obtain 40% Difficulty | +7% Difficulty. |
| Slippery Ring | Unlocked by default | +15% Evasion. |
| Slurp Gloves | Unlocked by default | Cast blood magic on hit; heals 7.5% with AoE burst, 9s cooldown. |
| Slutty Cannon | Kill 5,000 enemies with Slutty Rocket | 20% chance to spawn missiles on kill. |
| Soul Harvester | Survive the Final Swarm for 6 minutes | Killing an enemy summons 2 homing souls. |
| Spicy Meatball | Unlocked by default | 25% chance for attacks to explode, dealing 65% AoE Damage. |
| Spiky Shield | Unlocked by default | Gain +2 Thorns per 1% Armor and +10% Armor. |
| Speed Boi | Complete a stage with 2+ Boss Curses | On less than 50% HP, it can slow time and deal 2x Damage. |
| Sucky Magnet | Complete every Charge Shrine on a map | Periodically drags in all XP Shards. |
| Tactical Glasses | Defeat a Miniboss in 25s or less | +20% Damage to enemies above 90% HP. |
| Thunder Mitts | Unlocked by default | On hit, generate a lightning strike (10s cooldown). |
| Time Bracelet | Unlocked by default | Gives you +8% XP Gain. |
| Toxic Barrel | Kill 2,000 enemies with Poison damage | Releases a toxic cloud when hit. |
| Turbo Skates | Upgrade both Cooldown & Agility Tomes to Level 5 in one run | Move Speed converts to Attack Speed, max +40% per stack. |
| Turbo Socks | Upgrade the Agility Tome to Level 5 | Increases +15% Move Speed. |
| Unstable Transfusion | Unlocked by default | Has a +27% chance to apply Bloodmark on hit. |
| Wrench | Unlocked by default | Shrines charge 4 seconds faster and give +7.5% shrine rewards. |
| Za Warudo | Unlocked by default | On fatal damage, you can freeze time (one use). |