Spider-Man seeks Curt Connors' aid to help reverse the aging effects of the Vulture's talons. After absorbing Spider-Man's youth, and DNA, the Vulture mutates into the Man-Spider. The Scorpion grabs Dr. Farley Stillwell to seek a cure for his own mutation.

When Norman Osborn attempts to take over Toomes Aerodynamic, it makes Adrian Toomes furious who, using the Tablet of Time technology, starts stealing youth from anyone he touches, and suits up as the Vulture to destroy Norman Osborn.

Spider-Man and Blade put aside their differences in an attempt to prevent Morbius from using the Neogenic Recombinator to transform everyone into vampires like himself. They team up with Lt. Terri Lee, a detective who falls for Blade. During one attempt to stop Morbius, he kidnaps Aunt May and Felicia, causing Spider-Man and Blade to have a brief falling out.

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

With the Tablet of Time, Silvermane's youth is restored, but he continues to grow younger until he finally becomes an infant. Surprisingly, the Tablet is even able to revert The Lizard back to Dr. Conners. As the ordeal has caused his wife to leave him, Kingpin orders the Tablet gotten rid of.

An ancient artifact known as the Tablet of Time has been uncovered. Kingpin wants to sell it, while elderly Silvermane wants to use it to restore his youth. Each crime lord kidnaps a useful hostage and a useless hostage.

Spider-Man's horrifying genetic mutation reaches its culmination as he transforms 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.

Spider-Man drinks a serum that makes him grow four extra arms. Marvel anti-hero Punisher thinks Spider-Man is a crook and chases him around. Spider-Man finds out that Michael Morbius has turned into a vampire and is draining people's blood to survive. Spider-Man wants to help Michael, but the Punisher is trying to get rid of Spider-Man at the same time.

Dr. Mariah Crawford has developed a cure for Spidey's disease, but she's reluctant to give an untested serum to Spider-Man that may result in permanent loss of his powers or worse. But after an angry outburst from Spider-Man, she hands it over. Peter, at the ESU lab, is secretly observed by Michael Morbius, who then swipes the infected blood sample after Peter leaves for the night.

Wolverine catches up with Spider-Man, who is hot on the trail of the missing Hank McCoy. Meanwhile, Hobgoblin steals the mutant technology information that Dr. Landon had prepared for the Kingpin. However, is Dr. Landon actually working on the cure he claims to the public is possible; is he working on creating mutant soldiers for the Kingpin; or does he have his own sinister agenda planned?

Spider-Man begins to worry about his growing mutation. In order to seek a cure, he heads to the Xavier mansion, where he encounters the X-Men. A brief fight occurs, after which Spider-Man explains his plight to Xavier. Professor X tells Spider-Man that he cannot cure him, and he angrily leaves the mansion. Beast tells Spider-Man to go to Herbert Landon, who is working on a cure for mutants. Afterward, Landon's men capture Beast. While Spider-Man is watching Landon's demonstration, the facility is attacked by Hobgoblin. However, a mysterious force holds the ceiling in place long enough for Spider-Man to escape. Wolverine begins to worry about Beast's disappearance. He discovers that Beast spoke with Spider-Man before he disappeared, and sets out to find him (Spider-Man).

While dealing with the stunning revelation of his condition, Spider-Man finds himself dealing with the rash of mysterious robberies happening across town. As Peter Parker, he tries to get closer to Mary Jane, he discovers that she is being stalked by an ex-boyfriend who reveals himself to be the super-thief Hydro-Man who's obsessed at winning her back. Based on Amazing Spider-Man #212

The six supervillains cannot believe their eyes when Spider-Man walks into their trap at the warehouse. Spider-Man attempts to battle the six, but is captured, tied to a chair, and unmasked by the Insidious Six, but he manages to convince them that he is a fraud. At the same time, Dr. Conners has some important news about Spidey's condition.

In order to finally kill Spider-Man for his enemy, Silvermane, the Kingpin hires six of Spider-Man's most heinous villains (Rhino, Shocker, Doctor Octopus, Mysterio, Scorpion and the Chameleon) to take down Spider-Man. At the same time, Spider-Man has been experiencing brief periods of time where his powers temporarily vanish.