Two best friends discover a doorway leading to the hospital for super heroes.

When a strange illness gives Gus evil powers, Kaz and Oliver sneak him into the ER for treatment. Horace pretends to be Skylar's father for a parent-teacher conference.

Oliver enlists a mind-altering superhero named Neocortex to help him become more carefree and spontaneous like Kaz. When the brainwashed Oliver is too reckless during a crisis, Kaz is forced to step up and be the responsible one.

Wallace uses an optical image replicator to turn Clyde into an identical look-alike of Kaz in hopes that the disguised Clyde will trick Oliver into revealing the secret location of Mighty Med.

Kaz and Oliver are trapped in the ER by an evil Skylar and the Annihilator and the two villains plan on taking over the hospital and eventually, the world.

Kaz and Oliver find themselves ambushed by the Annihilator and Skylar Storm on Caldera. With the help of Hapax the Elder, the boys must find a way to take down the supervillains and save the world.