Each room contains several unique Sanctum Guards. All Guards must be killed before being able to complete the room.
| Guard type | Identifying features | Skills | 
|---|---|---|
| Entombing Warden | Coldsnap Bow | Ice Snipe, Cold Rain of Arrows | 
| Masked Combatant | Gray hood | Proximity Bomb, Smoke Mine, Mirror Image on Hit | 
| Azure Assassin | Arcane Lightning Helmet | Decelerating Projectile into Lightning Vortex, Galvanic Arrow | 
| Templar Marksman | Dragon Hunter Bow, Heritage Helmet | Dodge Roll, Flare Arrow, Blast Rain | 
| Infernal Sentinel | Dawnbreaker | Slash, Fire Thrust, Projectile Cleave , Shield Charge | 
| Obsidian Sentinel | Kongor’s Undying Rage | Consecrated Path, Summon Unholy Relic | 
| Crimson Archmage | Witchhunter’s Judgment, skull head | Flameblast, Fireball, Fire Twister | 
| Deathly Archmage | Skull head | Ice Spear Volley, Spike Wave, Ice Crash | 
| Undying Archmage | Mystic Staff, skull head | Projectile Bolt, Vorana orbs, Storm Burst | 
| Deadly Bladedancer | Crypt Sword | Sweep Cleave, Flicker Strike | 
Each room other than the miniboss room contains several Guard unique monsters, as well as one of three tasks to complete the room:
| Room Goal | Defeat all the Guards | Defeat all the Guards (Skull Arena) | Find the Exit | Find the Exit (Traps) | Defeat the Boss (Miniboss) | 
|---|---|---|---|---|---|
| Floor 1: Sanctum Archives | Chambers of Inscription | Templar Annals 1 central Skull, walls | Abandoned Library Ice Traps | Holy Trials Mana Rune Squares | Scriptorium Crimson Archbishop | 
| Floor 2: Sanctum Vaults | Derelict Caverns | Battlegrounds 1 central Skull, no walls | Decrepit Cellar Ice Traps | Gauntlet Rolling Exarch Boulders | Reliquary Greater Wraith | 
| Floor 3: Sanctum Cathedral | Unholy Lair | Infernum 2 Skulls, dividing wall | Halls of Worship Ice Traps | Crucible Mana Rune Squares and Skull | Sanctum Bellum Aureate Guardian | 
| Floor 4: Sanctum Necropolis | Lost Catacombs | Desecrated Crypt 1 Skull, 90 degree arc | Undercroft Ice Traps and Skull | Entombment Rolling Exarch Boulders or Mana Rune Squares + Lasers | Mausoleum Colossal Lithomancer | 
Note: most “Find the Exit” rooms have shortcuts that require movement skills.