Three years following the events of "Doctor Who and the Marvelous Muppets," the Earth-M universe has become a haven for weirdness and mayhem, which is normal for a world where Muppets, aliens, wizards, and superheroes coexist. However, the sudden arrival of Seana (an incarnation of Neas, the Gladiator of Gallifrey) brings Sean Livingston, the new director of S.W.O.R.D., into a multiverse of madness. But the further down the rabbit hole this mystery goes, the bigger it turns into an Avengers-level threat.