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

When Oliver's dad starts to wonder where he's going after school, Oliver says he's doing a play about Frankenstein.

Kaz boldly asks the most popular girl in school to the upcoming school carnival but is rejected, and tries to save face by claiming he already has a girlfriend. Much to Oliver's chagrin, Kaz invites Skylar to accompany him to the carnival, her first venture into the "normo" world, in hopes of convincing everyone that she is his girlfriend. Meanwhile, Alan tries to prove his worth to his uncle Horace by attempting to cure Titanio, a superhero with amnesia.

Oliver uses his burgeoning medical skills at school when he performs CPR on a popular girl's poodle, which quickly elevates his social status much to Kaz's chagrin. When the popularity goes to his head, Kaz cuts Oliver down to size, literally, with a shrinking ray. Meanwhile, Horace cannot perform surgery on Citadel, an ailing superhero with an impenetrable metal exoskeleton, so shrunken Oliver is sent inside the hero's body to diagnose the problem.

When Kaz and Oliver learn that pranks do not exist in the world of their superhero friend Skylar, they set out to teach her how to prank.. When The Great Defender joins in, he takes the pranks too far and wreaks havoc on the hospital.

When Kaz and Oliver meet Timeline, a superhero who has the ability to see into the future, they discover that villain Crimson Demon and his three brothers have a plan to destroy the world. Oddly enough, because Kaz whizzed through his pop quiz, these three events lead to a portal's opening for the freedom of Crimson Demon's brothers. The three events are: the fool will become the wise man (Kaz whizzing the pop quiz), knight will fall during the day (Oliver falling inside a knight costume), and the chord of dischord will be played (Gus). [1]

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.

Alan is put in charge of the hospital for a day, but he abuses his power and makes life miserable for everyone.

Kaz applies to be Tecton's sidekick, but Oliver is chosen instead. Alan and Benny form a superhero team of their own.

Kaz plans a surprise birthday party for Oliver and accidentally lets in the villain Revengeance.

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.

Skylar introduces Kaz and Oliver to her longtime friend Experion, a cool and charming teenage superhero. But when Oliver catches Experion in an evil act, he must convince Skylar that her bestie is not as nice as he seems.

Kaz and Oliver revive a frozen-in-time superhero from the 1950s named Captain Atomic. After Captain Atomic is wounded during a battle with a contemporary villain, the boys must travel back in time to save him.

Oliver accidentally steps into the line of fire of a superhero's beam during a routine test, which reverts him back to being 4 years old. While Kaz tries to fix Oliver, Alan develops an undesirable and embarrassing power.

Kaz and Oliver are exhausted and stuck working the overnight shift during a lunar eclipse, when it is rumored that the freakiest patients come to the hospital. When Neocortex checks in with an illness that unintentionally traps people in their worst nightmares, Kaz and Oliver desperately try to stay awake and figure out how to save everyone from their nightmares.

Tension is high at Logan high, and Kaz becomes suspicious that his substitute teacher is actually Dr. Wrath in disguise, a supervillain who feeds on negative energy. While Kaz is determined to get to the bottom of it, Oliver helps Alan get over his aversion to normo food.

Kaz's fantasy football team always loses, so he get's upset since he never wins at anything. But when Tecton rescues Oliver from another superhero's snot rocket, Kaz makes up a fantasy superhero league. At first, it's a success, but when everybody goes to stop a runaway Ferris wheel for points, a villain named Sonic Shriek gets the chance to destroy the Benjamin Franklin bridge, and two superheroes, Tecton and Captain Atomic, turn on each other. Thankfully, Sonic Shriek's plan is foiled by Tecton, Captain Atomic, Skylar, and Kaz. Meanwhile, Oliver teaches Horace about Normo football. When Alan says he knows more about football than Oliver, they settle their differences with a trivia contest. However, Oliver is distracted by Alan's partner, Adrian Peterson. In the end, Oliver and Horace lose, so they have to sing a song about Alan.

Kaz and Oliver must study for a Mighty Med exam that will allow them to learn deeper secrets of Mighty Med, but if they fail, they will be cubed. Meanwhile, Wallace uses an optical image replicator to turn Clyde into an identical look-alike of Kaz. Clyde successfully follows Oliver into Mighty Med, but when he tries to steal the missing half of the Dyad of Nebulon, Horace senses something is amiss, and sends the guards after him, just as the real Kaz walks back into Mighty Med. Horace catches a Kaz and thanks to Oliver, doesn't cube him, but erases his memory. The guards send out the Kaz, and the other Kaz appears. Oliver realizes that this Kaz is the real Kaz, and the other one was really Clyde (though he doesn't know its Clyde). Horace explains that the other half of the dyad is with a villain named Catastrophe, who upon being defeated split into two humans (Wallace and Clyde). Back at The Domain, Wallace is trying to recall Clyde's memory of Mighty Med, which was successfully wiped. Kaz and Oliver pass their exam, and learn the secrets of Mighty Med. Meanwhile, when Alan comes to Skylar for advice on a girl he likes, she suspects it's her, and tries to dissuade him, only to learn it was a nurse who's also an octopus.

When a freak accident suddenly gives edgy rock star Jade super powers at a concert, attendees Kaz and Oliver recognize a new hero in her, and introduce her to Mighty Med. Jade becomes the hero Remix with Kaz and Oliver's help, but Skylar isn't convinced she's a hero when she's very demanding of service. Skylar decides to teach her a lesson by having Titanio dress like Soul Slayer, a teleporting villain, to attack her during rehearsal. When the real Soul Slayer arrives, Jade must become a real hero to save a powerless Skylar from Soul Slayer. Meanwhile, Jordan and Gus learn they will be dissecting frogs in class and Jordan plots to steal it to save it from dissection, but when they attempt to retrieve Gus' ransom note, their teacher catches them and reveals that when she discovered it was gone, she assumed they were trying to save it and told a local animal rights organization who will give the savior one thousand dollars, which goes to Gus since Jordan made him take the blame, much to her disappointment.

Kaz hasn't read his reading book again, so he decides to copy Oliver's study guide, which is on his flash drive.

When Horace complains that comic book sales are down, Oliver and Kaz join the writing staff to help spice up the books. However, the boys' altered versions of the stories cause problems in the superhero community.

Oliver and Skylar pet sit Horace's shark that is kept in the aquatic wing of the hospital. When Oliver feeds the shark the wrong food, the shark evolves into a man-shark.

Horace introduces the boys to an all-powerful device that looks like a pen, but can bring any illustration to life. Panic ensues at the hospital when the device goes missing.

It has been nearly 1 year since Skylar, Kaz and Oliver became friends and Kaz and Oliver throw a party to celebrate their friendship. However, the boys learn not only is Skylar is in danger of losing her powers forever but she will also die. The boys help Skylar when in order for Skylar to reclaim her powers, she has to fight her nemesis The Annihilator.