When Spider-Man discovers Max Modell is experimenting with a synthetic version of the Venom symbiote, he warns him of the dangers. When Curt Connors stumbles on the experiment, he accidentally releases the real symbiote.
Discovering a vial of the Jackal formula at Horizon High, the Spider Team realizes that the Jackal has returned since the Spider Island crisis. Spider-Man and Ghost-Spider track down Jackal's secret lab in an attempt to thwart the villain's latest evil plans.
When Spider-Man and his allies attempt to track down the missing and dangerous Lizard, they discover that Venom has returned to seek revenge on the earth.