The Punisher comes to New York to deal with the mutating Spider-Man, who has just grown four extra arms, and is in search for also mutated Morbius who is killing (eating) innocent people, and the people of New York blame Spider-Man for all that is happening.

After Spider-Man mutates into the Man-Spider, Dr. Mariah Crawford summons Sergi Kravenoff, better known as Kraven The Hunter, to help her track down Spider-Man and cure him of his mutation with a newly developed antidote. Unfortunately, the Punisher is hot on Spidey's heels. Will the Punisher succeed in destroying Spider-Man in his new mutated form or will Kraven and Dr. Crawford reach him first?

Harry Osborn is haunted by dreams of his father, the Green Goblin, and Spider-Man. The Goblin visits him and guides him to the Goblin formula and weapons. Meanwhile, the Punisher promises Anna Watson that he will find Mary Jane, and top of his list of suspects is...Peter Parker?!