Monstro II is a posthumous version of Monstro which can be encountered in the first level of The Depths or Necropolis. He appears as Monstro's skull, with only a portion of flesh still attached to his face. If the player has defeated Monstro in The Basement, the chance to meet him is higher. Monstro II has a chance to be replaced by Gish.
Besides having increased HP, Monstro 2 differs by the following:
- His vomit has been upgraded to a Brimstone/Shoop Da Whoop!-style laser that he shoots left or right (look for him to grin before he fires).
- His launch in the air attack has new effects. The first time he lands, he will spawn very large 8 direction shots. These deal a full heart of damage. The second time he launches and lands, he spawns four Suckers which explode into projectiles in the four cardinal directions. These 2 effects alternate in order, and he always launches twice in a row.
Having the Halo Of Flies or similar orbiting items will greatly increase survivability in this fight. Otherwise, just keep on the run to avoid the increased projectile fire.
Unlike Monstro, standing near to Monstro II will make it more likely that he will use his laser or hop towards you. This can make the fight significantly easier to manage, as he is much easier to hit when he isn't continually jumping or spawning flies.
Since Monstro II always does the huge jumps twice in a row, you can use this to your advantage - on every second launch, drop a bomb before moving. When Monstro II lands and spawns Suckers, the bomb will explode, destroying most of the Suckers and dealing significant damage to the boss himself.
An easy way to defeat him is to stand in front of him until he grins, then quickly run behind him before he triggers his blood vomit beam, then attack until he grins again. If done correctly, Monstro II will be defeated without giving him a chance to do his annoying leaps. A somewhat less risky strategy would be to get out of the way when Monstro II vomits, then quickly get back in the way when the attack ends and take a few quick shots at him until he grins again.
It's also possible to get him stuck against the geometry of the bottom of the room and stand in such a way that his blood beam will not hit you, but still be close enough to cause him to only use this attack. If you can stand there and attack him, he will be continuously pushed against the geometry behind and below him, holding him in this sweet spot. Great for characters with low damage or speed and need to just sit there and whack at him for a while.
Monstro II becomes twice as fast and spawns only 2 Suckers on his second jump.
- There is a bug with the champion variant of Monstro II where he sometimes jumps three times shooting out 8-way shots before jumping and spawning Suckers. 
- If Isaac has more than one life (through Dead Cat, 1UP or Ankh) and dies inside the boss room after defeating Monstro II, instead of Monstro II respawning fully, only two Attack Flies will spawn. Killing the flies will count as if you killed Monstro II again and will reward you with a boss room item.
- In his Boss Art, his eye looks "normal", being beady and black. In game, however, it is a sick, pale color.
- Like Monstro, Monstro II is missing a tooth. This can be assumed to be the source of Monstro's Tooth.
|Basement||Larry Jr. • Monstro • The Duke of Flies • Gemini • Steven • Famine|
|Cellar||Widow • Pin • The Duke of Flies • Famine • Gurdy Jr. • The Blighted Ovum|
|The Caves||Fistula • Peep • Gurdy • Chub • C.H.A.D. • Pestilence|
|Catacombs||The Husk • The Hollow • The Blighted Ovum • The Carrion Queen • Peep • Pestilence • The Wretched • Gurdy Jr.|
|The Depths||Loki • Monstro II • Gish • War • Mom|
|Necropolis||Mask of Infamy • Daddy Long Legs • The Carrion Queen • The Bloat • Loki • War • The Wretched • Mom|
|The Womb||Scolex • Blastocyst • The Bloat • Death • Conquest • Daddy Long Legs • Triachnid • Teratoma • Mom's Heart • It Lives|
|Utero||Teratoma • The Bloat • Death • Conquest • Daddy Long Legs • Triachnid • Lokii • Mom's Heart • It Lives|
|Sheol||The Fallen • Satan|
|First to fifth and seventh level||The Fallen • Headless Horseman|