Norman Osborn hires Spencer Smythe to design a machine capable of destroying Spider-Man - the Black Widow Spider Slayer. But when Flash Thompson puts on a Spider-Man costume as a party gag, the deadly machine spots him, and he's carried off in Peter's place.

With Spencer Smythe dead, his son Alistair turns to the Kingpin to help seek his revenge on Spider-Man and others he deems responsible for his father's death. He captures, Eddie Brock, J. Jonah Jameson, Norman Osborn, and Flash Thompson. He then turns his sights on Spidey and sends three slayers after him. Spidey only manages to hold his ground while fighting them individually. However, he is not so lucky when they combine into a super slayer and carry him off to Smythe.

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.

Norman Osborn hires hitman and thief, the Hobgoblin, to take out Osborn's "silent" partner, Wilson Fisk (the Kingpin). When he fails in the attempt, the Hobgoblin changes sides, kidnapping Norman's son, Harry. Harry just happens to be best friends with Peter Parker.

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.

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.

The six supervillains can't believe their eyes when Spider-Man walks into their trap at the warehouse. But it's obvious why, when they easily overcome and unmask the fraud. Meanwhile, Silvermane and the Crime Lords grow more disenchanted with The Kingpin and want to put him out of business. Kingpin beats them to the punch, kidnapping Silvermane. Can Spider-Man save the day?

Spider-Man's progressing neogenic mutation is making him ill and he seeks the aid of a man known to help all mutants...Dr. Charles Xavier. In doing so he meets the X-Men but is disappointed to learn that Xavier does not 'cure' mutancy, only helps those born that way to accept and control their abilities. In the process of this endeavor though he becomes involved in a plot to destroy mutants everywhere. Will he be able to stop this hideous plan with the help of the X-Men?

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?

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.

With the Tablet of Time, Silvermane's youth is restored, but he continues to grow younger until he finally becomes an infant.

Spidey and Daredevil manage to recover the disk that can clear Peter Parker's name. However when Matt Murdock hands the disk over to the FBI, Det. Terry Lee discovers Agent Choi may not be working for the right side when she hands it over to Richard Fisk. After learning that Aunt May is in the hospital, Peter risks his life to go visit her, but he and Mary Jane are kidnapped when the Chameleon disguises himself as Anna Watson. With Peter and the disk in the hands of the Kingpin, Daredevil must stop the criminal mastermind and clear Peter's name.

Worried that Kingpin is going to eliminate him after the botched framing of Peter Parker, Alistair Smythe arranges a meeting with Spider-Man to give him information about Kingpin. However, when Spidey arrives, he discovers Smythe has been turned into a cyborg. Part man, part machine, he is now the ultimate spider-slayer! However, when his programming malfunctions, he goes after the man he feels responsible for his father's death...Norman Osborn! Peter must fight a crazed Smythe, as well as his feelings when he discovers Mary Jane, the woman he loves, and Harry, his best friend, are engaged!

While settling in to her new role as a hero, the Black Cat is captured by Allistair Smythe, now working for Silvermane, who is trapped in the body of a baby. Smythe delivers Spidey an ultimatum: capture the Scorpion or the Vulture within 24 hours or the Black Cat dies...

Peter and MJ's big day arrives, but things aren't going to go to plan if Harry Osborn gets his way. With guests including Flash Thompson, Liz, Aunt May, Anna Watson, Felicia Hardy, J. Jonah Jameson, Robbie Robertson and Wilson Fisk!? Along with gate crashers including the Green Goblin, the Kingpin, Alistair Smythe, the Scorpion, the Black Cat, Herbert Landon, the Mega-Slayer, Norman Osborn, and an army of robot Goblin Warriors, it'll certainly be a day to remember!

Spider-Man summons the Black Cat from earth, who despite her anger at being kidnapped, decides to help him fight the villains on the alien planet. The heroes must defeat the Red Skull, Doctor Octopus, and Allistair Smythe's robots while protecting a group of rebels, who are trying to take their planet back.