J. Jonah Jameson hires Dr. Farley Stillwell who is a raining genius in genetic engineering, to make a new super hero that can match and defeat Spider-Man. With a willing participant, Mac Gargain, they engineer the DNA of a scorpion and him together to form a new hero, The Scorpion. However, when Mac thinks they have turned him into a freak, hero turns to monster and he goes on a rampage. Spider-Man is then forced to step in to stop creation from killing creator.

The Crime Lords, led by Silvermane, are holding The Kingpin accountable for his failure to eliminate Spider-Man. So six of the Wall-Crawler's greatest enemies are called together to do the job: Doctor Octopus, Mysterio, The Scorpion, The Rhino, The Shocker and The Chameleon. Unfortunately, Spidey's powers have been on the blink due to the changes in his blood chemistry.

Spider-Man seeks Curt Connors aid to help reverse the aging effects of the Vulture's talons. The Vulture meanwhile sporadically turns into the man-spider from the mutagenics he absorbed with Spidey's youth. At the same time, the Scorpion grabs Dr. Farley Stillwell to seek a cure for his own mutation. With Doc Connors in the middle, feeling the onset of his own his reptilian transformation, will everyone be cured in time for Peter to meet up with Mary Jane as she confronts her wayward father???

Tired of Jameson giving Spider-Man the rap for all the crime in New York, Peter decides to give up the superhero business once and for all, until he meets his biggest fan, a little girl named Tyina. Can she get Spidey to change his mind?