Optimal Path to finish a Dead God run — Checklist
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Miscellaneous Unlocks
Donation Machine: prioritize upgrading for better shops.
The Lost: die in a sacrifice room while holding Missing Poster.
Ace of Clubs: win three runs in a row.
Super Tinted Rocks: win five runs in a row with separate characters.
The Halo: defeat Mom or It Lives with The Bible.
Gulp! Pills: complete a Victory Lap.
Marbles: use 5 Gulp! pills in one run (cheeseable in Greed with Lazarus).
Huge Growth: increase size 5 times in a run.
Counterfeit Penny: play shell/hell game 100 times.
Planetariums: obtain 2 tarot/zodiac items in one run.
Tech 0: obtain 2 robo-baby/technology items in one run.
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Daily Runs
Cracked Crown: get a 5-win streak in daily runs.
Broken Modem: complete 7 daily runs.
Horf! pill: participate in 31 daily runs.
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Things to avoid
Corrupted Data: Defeat Delirium with Tainted Eden (very bad).
Re-lax / ??? pills: Complete Challenge #25: Have a Heart.
Rules Card: Complete Challenge #11: Glass Cannon.
Suicide King: Complete Challenge #7: Suicide King.
Scared Hearts: Reset 7 times in a row.
Scissors: Die 100 times.
Various bad Boss Rush / challenge combos (Missing No., Isaac's Head, etc.).
Shade / Berkano / TMTRAINER / Torn Card / IBS — avoid until you understand consequences.
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Runes to unlock first
Jera: complete challenge #2 - High Brow (unlocked at start).
Ehwaz: complete challenge #3 - Head Trauma (unlocked at start).
Ansuz: challenge #5 - The Tank (7+ heart containers / Magdalene).
Blank/Clear Rune: challenge #30 - The Guardian (defeat Mom).
Perthro: challenge #6 - Solar System (defeat Mom's Heart 3x).
Dagaz: challenge #4 - Darkness Falls (defeat Mom's Heart 11x, ??? as Eve).
Algiz: challenge #8 - Cat Got Your Tongue (become Guppy).
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Challenges to finish asap when unlocked
A Card Against Humanity: #12 - When Life Gives You Lemons (start).
Burnt Penny: #13 - Beans! (start).
SMB Super Fan: #14 - It's in the Cards (start).
Death's Touch: #17 - Waka Waka (start).
Technology .5: #18 - The Host (start).
Chaos Card: #9 - Demo Man (defeat Mom's Heart 9x).
Credit Card: #10 - Cursed! (unlock Magdalene).
Epic Fetus: #19 - The Family Man (both angel key pieces in one run).
Sigil of Baphomet: #37 - Bloody Mary (unlock Bethany, Blood Bag, It Lives).
VIII - Justice?: #43 - Cantripped (unlock Tainted Cain).
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Early progression / mechanic unlocks
Lucky Pennies: donate 2¢ to Greed donation machine (Azazel to also unlock Lilith).
Store Upgrade 1: donate 20¢ to donation machine.
Polaroid: defeat Isaac 5 times (need angel deals).
Negative: defeat Satan 5 times (need devil deals).
The Void: defeat Hush (requirements: beat Mom's Heart 10x & then within 30 minutes).
Missing Poster: defeat The Lamb as Isaac (need Negative).
Corpse: defeat Hush 3 times.
Dad's Note: defeat Mother.
Greedier Mode: donate 500 coins to greed donation machine.
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Character Unlocks
Magdalene: have 7+ red heart containers.
Cain: hold 55 coins.
Eve: don't pick up any hearts for 2 floors in a row.
Samson: complete 2 floors in a row without damage.
Azazel: make 3 deals with the devil in one run.
Lazarus: have >4 soul hearts at once.
Judas: defeat Satan.
Eden: complete chapter 4 (Womb).
Bethany: defeat Mom's Heart/It Lives on Hard as Lazarus without dying.
???: defeat Mom's Heart 10 times.
The Lost: die in a sacrifice room while holding Missing Poster.
Lilith: defeat Ultra Greed as Azazel.
Keeper: donate 1000 coins to greed donation machine.
Apollyon: defeat Mega Satan.
The Forgotten: requires Negative unlocked.
Jacob & Esau: defeat Mother (need Corpse unlocked).
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Early Completion Marks
Isaac starts with D6: defeat Isaac as ???.
Mom's Knife: defeat Satan as Isaac.
Missing Poster: defeat Lamb as Isaac.
D20: defeat ??? as Isaac.
D Infinity: defeat Delirium as Isaac.
The Relic: defeat Isaac as Magdalene.
Purity: defeat Hush as Magdalene.
Eucharist: defeat Delirium as Magdalene.
Judas' Shadow: defeat Boss Rush as Judas.
The Nail: defeat Boss Rush as Azazel.
Pandora's Box: defeat Lamb as Lazarus.
Empty Vessel: defeat Hush as Lazarus.
Book of Secrets: defeat Satan as Eden.
Blank Card: defeat Isaac as Eden.
Succubus / Incubus / Euthanasia / C Section (Lilith rewards).
Smelter / Void (Apollyon rewards).
Compound Fracture: defeat Delirium as Lazarus.
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Tainted Character Unlocks
Unlock tainted characters using cracked key/red key in left Home hallway.
Unlock while regular character fights The Beast; order not important.
Recommendation: wait until many early completion marks are done; avoid The Lost until Greed donation gives Holy Mantle.
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Greed(ier) Mode
Donate early with Azazel to unlock Lilith (lucky pennies, hanging shopkeepers).
Donate 500 coins to unlock Greedier Mode.
Greed donation unlocks overview: Wooden Nickel (33), Paperclip (68), Everything is Terrible 2 (111), Special Shopkeepers (234), Razor Blade (439), Greedier (500), Store Key (666), Lost Holy Mantle (879), Keeper (1000).
After Greedier unlocked: prefer Greedier mode due to lower jamming risk; consider delaying finishing until Keeper/Lost/Tainted unlocks completed.
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Miscellaneous Unlocks 2
Ace of Diamonds: defeat the Lamb within 20 minutes.
Ace of Spades: defeat the Lamb without picking up any heart, bomb, or coin.
Redemption: unlocked via specific Judas confessional/angel room manipulation (beat The Beast with Judas).
Plum Flute: avoid hurting Baby Plum ~30s in boss fight; she flies away and leaves the item.
Charged Penny: donate to battery bums until items pay out 5 times.
Moving Box: use Pandora's Box in Dark Room.
Blinding Baby: use Blank Card while holding XIX - The Sun.
Brimstone Bombs: defeat Hornfel in the Mines and kill him before he escapes.
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Later Completion Marks
Crane Game: defeat Mega Satan as Tainted Samson.
Strange Key: defeat Lamb/??? as Tainted Eve.
Golden Penny: defeat Mega Satan as Tainted Keeper.
Confessional: defeat Mega Satan as Tainted Bethany.
Keeper holds Wooden Nickel: defeat Isaac as Keeper.
Godhead: get all completion marks on Lost on Hard mode.
Various tainted Mega Satan / Beast / Delirium rewards (see guide for specifics).
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Quality of Life Mods I use
External Item Descriptions (AB+|Rep(+)): improved in-game descriptions.
Range fix for Bones & Sword: bugfix for melee/range interactions.
Coming Down! [Rework]: shows stomping attack icons (accessibility).
Silent Dog Tooth: helps when playing without audio.
Boss Rush Wave Counter, Enhanced Boss Bars, cosmetic or small QoL mods.
Mod Config Menu Pure: used to configure other mods.