Spider-Man embarks on a risky mission, when he learns that a Horizon High student is conducting experiments on a version of the Venom symbiote, whereupon he and Max Modell try to stop Venom from destroying the planet, as Curt Conners releases the latter unwittingly.
When Groot lands on Earth looking for Spider-Man to deliver a message to, the latter has to decipher the message and keep Groot away from A.I.M’s reach.
During an attack by symbiotes on New York, Spider-Man tries to find a way to stop them, so he turns to Marc Spector, a retired superhero.
When Spider-Man finds out that Swarm turned his friend back into Rhino, he intervenes, after which he’s forced to enter a contest called the Underground Monster League.
As Spider-Man happens on a vial containing the Jackal formula, he and Ghost-Spider set out to locate Jackal’s secret lab to prevent him from carrying out his evil plans.
As Spider-Man and his friends try to find where the missing Lizard is, they learn of Venom’s return to destroy Earth.