| Achievement | How to unlock
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| - Complete America's Newest Legacy's story challenge to unlock the variant. (Secret)
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| - Defeat all core game Villains on Challenge Mode.
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| - Variety is the spice of pain! Deal 100 damage of each type across all battles.
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| - Complete Cosmic Omnitron's story challenge to unlock the variant. (Secret)
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| - Complete Dark Watch NightMist's story challenge to unlock the variant. (Secret)
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- Extreme Hostage Situation
| - This IS a card game, right? Defeat any Villain without a hero card entering play the entire battle.
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| - Achieve victory without a scratch. Win a battle with all Heroes at full HP.
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| - Completed Freedom Six Unity's story challenge to unlock the variant. (Secret)
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| - Complete Freedom Six Wraith's story challenge to unlock the variant. (Secret)
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| - Complete G.I. Bunker's story challenge to unlock the variant. (Secret)
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| - Unleash a large barrage. Deal 20 damage or more in a single attack.
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| - Spread the love of Sentinels online. Play a multiplayer game with Handelabra Games, Greater Than Games, or someone who has.
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| - Complete Mad Bomber Blade's story challenge to unlock the variant. (Secret)
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| - Did you bring the band-aids? Restore 200 HP to hero targets across all battles.
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| - It can make you feel so powerless. Defeat any Villain without using powers the entire battle.
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- Prime Wardens Argent Adept
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- Prime Wardens Captain Cosmic
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| - Win a battle in each core game Environment.
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| - Who are you even aiming at? Redirect a single instance of damage at least 5 times.
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| - Complete Rook City Wraith's story challenge to unlock the variant. (Secret)
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| - You won't get away with it this time! Defeat 10 Nemeses with the nemesis dealing the final blow.
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| - Complete Skinwalker GloomWeaver's story challenge to unlock the variant. (Secret)
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| - Complete Spite: Agent of Gloom's story challenge to unlock the variant. (Secret)
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- Termi-Nation Absolute Zero
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| - Win a battle by the skin of your teeth - a single hero standing, with only 1 HP remaining.
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| - Complete The Eternal Haka's story challenge to unlock the variant. (Secret)
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| - Defeat all core game Villains on Advanced.
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| - Defeat all core game Villains.
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- The Scholar of the Infinite
| - Complete The Scholar of the Infinite's story challenge to unlock the variant. (Secret)
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- The Super Scientific Tachyon
| - Complete The Super Scientific Tachyon's story challenge to unlock the variant. (Secret)
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| - Defeat all core game Villains on Ultimate Mode.
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- Xtreme Prime Wardens Argent Adept
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- Xtreme Prime Wardens Captain Cosmic
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- Xtreme Prime Wardens Fanatic
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- Xtreme Prime Wardens Haka
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- Xtreme Prime Wardens Tempest
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