A space shuttle piloted by J.J.'s son, John Jameson, crash lands on the Tri-Borough Bridge carrying two strange meteors -- One that could provide a new nuclear fuel and one that contains an alien substance. The first is stolen by the Kingpin's henchman, the Rhino, just as Spider-Man arrives to save Jameson and the co-pilots. When the Rhino sends the aircraft off the bridge, Spider-Man emerges from the water with a dark stain covering his costume. Exhausted, he heads for home, only to awaken hanging from a skyscraper, now clothed in a black version of his costume.

When Aunt May is slightly injured by one of the Hobgoblin's pumpkin bombs during the kidnapping of Harry, Spider-Man enters the fray with a vengeance. After several battles, the trail leads Peter to Oscorp and Harry's own father. For Peter, rescuing his friend is easy compared to explaining to Harry that his own father is involved.

Wolverine catches up with Spider-Man, hot on the trail of the missing Hank McCoy. Discovering his location and the plot to destroy all mutantkind the two team up and rescue Beast in the nick of time just as he was about to become the first test subject of Landon's horrendous plan. But when Landon accidentally falls victim to his own experiment he is changed into a giant monster that feeds on electrical energy. Can Spider-Man and the X-Men succeed in stopping this 50-foot tall, ohm-eating monster?

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?

The vampire hunter Blade arrives in New York to destroy Morbius, but Spider-Man wants to revert Morbius back into his human form.

Dr. Curt Connors is set to study the Tablet of Time, a recently discovered ancient artifact that is said to restore a person’s youth. Dr. Connors believes that it can cure Spider-Man’s mutagenic transformations with the tablet.

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.