Many thousands of years in the future, Earth’s cities roam the globe on huge wheels, devouring each other in a struggle for ever diminishing resources. On one of these massive traction cities, the old London, Tom Natsworthy has an unexpected encounter with a mysterious young woman from the wastelands who will change the course of his life forever.

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.

After reuniting with Gwen Stacy, Brooklyn’s full-time, friendly neighborhood Spider-Man is catapulted across the Multiverse, where he encounters the Spider Society, a team of Spider-People charged with protecting the Multiverse's very existence. But when the heroes clash on how to handle a new threat, Miles finds himself pitted against the other Spiders and must set out on his own to save those he loves most.

Puss in Boots discovers that his passion for adventure has taken its toll: He has burned through eight of his nine lives, leaving him with only one life left. Puss sets out on an epic journey to find the mythical Last Wish and restore his nine lives.