Spider-Man goes after Eddie Brock for labeling him as he is now being stalked by bounty hunters at every turn. After being reassured by Mary Jane that he has changed, he seeks help from Dr. Curt Connors who discovers that the suit is alive!! And Peter is the host organism!

The Kingpin is furious at Spidey and sends the Shocker and later the Rhino out to finish him off with the aid of another new invention of Alistair Smythe. Meanwhile, Eddie Brock, as the symbiote creature Venom, is busy playing cat and mouse with Spider-Man, intruding on Peter's private life and making it clear he knows the web-slinger's secret identity. Peter soon realizes that the pumped-up Eddie as Venom is stronger than he is. Worse than that: Spidey's spider-sense doesn't work around him!

Under the psychiatric care of Dr. Kafka, Eddie Brock has come to believe that Venom is a figment of his imagination. Then Baron Mordo tempts Eddie -- reunification with the alien symbote that makes him as powerful as Venom.

Spider-Man and Venom must put aside their differences and help Iron Man stop Carnage and Baron Mordo from releasing Dormammu.