Struggling to find his place in the world while juggling school and family, Brooklyn teenager Miles Morales is unexpectedly bitten by a radioactive spider and develops unfathomable powers just like the one and only Spider-Man. While wrestling with the implications of his new abilities, Miles discovers a super collider created by the madman Wilson "Kingpin" Fisk, causing others from across the Spider-Verse to be inadvertently transported to his dimension.

King T'Challa returns home to the reclusive, technologically advanced African nation of Wakanda to serve as his country's new leader. However, T'Challa soon finds that he is challenged for the throne by factions within his own country as well as without. Using powers reserved to Wakandan kings, T'Challa assumes the Black Panther mantle to join with ex-girlfriend Nakia, the queen-mother, his princess-kid sister, members of the Dora Milaje (the Wakandan 'special forces') and an American secret agent, to prevent Wakanda from being dragged into a world war.

After the re-emergence of the world's first mutant, world-destroyer Apocalypse, the X-Men must unite to defeat his extinction level plan.