Wolverine catches up with Spider-Man, who is hot on the trail of the missing Hank McCoy. Later Hobgoblin steals the mutant technology that Dr. Herbert Landon had prepared for the Kingpin. Spider-Man and Wolverine follow him and discover Beast's location as well as the plot to destroy all mutant-kind; the two team up and rescue Beast from becoming the first test subject of Landon's plot. But when Landon accidentally falls victim to his own experiment he is changed into a giant monster that feeds on electrical energy.

Spider-Man's mutation is now turning him into a monster. Luckily for Peter, Dr. Mariah Crawford has developed a possible cure for the disease. But before the cure could be implemented, Morbius steals a sample of Peter's blood. While experimenting on the sample, a vampire bat bites Morbius and causes a mutation that will change him forever.

Spider-Man's progressing neogenic mutation is making him ill. He approaches Professor Charles Xavier to help him find a cure. In doing so he meets the X-Men but is disappointed to learn that Xavier does not 'cure' mutancy, and only teaches mutants how to control their abilities. But before Spider-Man leaves, Beast tells him about Dr. Herbert Landon who is working on a cure for mutants. Desperate for a cure, Peter Parker attends one of Landon's demonstrations only to find himself in a death match between himself, Wolverine and the Hobgoblin!

Spider-Man's mutation is getting worse and causes four additional arm to grow on his body. As Morbius's rampage continues, the Punisher comes to New York to deal with the mutating Spider-Man, blaming him for the attacks that Morbius is perpetrating.

Mary Jane's old boyfriend begins stalking her. He has a new ability to transform his body into water and is furious over Mary Jane's relationship with Peter Parker. As his rage builds up, Hydro-Man becomes more and more dangerous. Spider-Man swings into action to protect Mary Jane and defeat the jealous ex-boyfriend.

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. But before he can study it, Silvermane steals the tablet and sends Spider-Man and Dr. Connors into a race to take it back.

The Insidious Six unmask Spider-Man, but Dr. Octopus is convinced that the Spider-Man they unmasked is a fraud. Meanwhile, Kingpin kidnaps Silvermane and, using the Insidious Six, wages war with the top crime lords in the city.

In addition to dealing with his best friend taking his girl out on the town, Spidey has to battle both Blade and Morbius. With the frenzied vampire hunter after the misunderstood living vampire and innocents caught in the cross-fire, Spider-Man has his work cut out for him!

In order to finally kill Spider-Man, the Kingpin hires the Insidious Six (Doctor Octopus, Scorpion, Chameleon, Shocker, Rhino and Mysterio) to take him down. Farley Stillwell also creates Neogenics, which starts taking away Spider-Man's strength. After losing his powers, Spider-Man is captured by the Insidious Six.

The vampire hunter Blade arrives in New York to destroy Morbius, but instead of killing him Spider-Man wants to revert Morbius back into his human form. When Spider-Man reveals that Morbius is the victim of a Neogenic Recombinator experiment gone awry, Blade decides to destroy the equipment. But before he can, Morbius steals it giving him the power to turn anyone into a vampire!

Spider-Man goes after the Hobgoblin after he attacks Aunt May and kidnaps Harry Osborn. He forms an alliance with Norman Osborn and unknowingly becomes allied with the Kingpin as well. After rescuing Harry, Spider-Man finds himself in an all-out no-holds-barred fight to the finish with the Hobgoblin.

Silvermane has possession of the Tablet of Time and plans to use it to restore his youth. He sends Tombstone to kidnap Dr. Connors to figure out how to channel enough energy for the tablet to work. Meanwhile, Kingpin sends Hammerhead to kidnap Alicia Silver as a bargaining chip to get his wife back from Silvermane. With a war between the two titans of the underworld about to explode, Spider-Man must find a way to save all the hostages while making sure the Tablet of Time is returned to the right hands.

Norman Osborn hires the the Hobgoblin to take out Wilson Fisk, but when he fails Osborn fires him. To get revenge on Osborn, Hobgoblin changes sides and kidnaps Norman's son, Harry, for the Kingpin.

When Norman Osborn attempts to take over Toomes Aeronautical, Adrian Toomes, using the Tablet of Times to steal youth from anyone he touches, suits up as the Vulture to destroy Norman Osborn!

Eddie Brock, now bonded with the symbiote costume and calling himself Venom, sets out to destroy Spider-Man. Now faced with a stronger foe that possesses the same abilities as him, Spider-Man must find a way to outwit and outmatch this menacing new villain and send the alien symbiote back to outer space.

Peter's search for Mary Jane leads him to an evil cult led by a man called Baron Mordo, who wants to release his master, Dormammu, from another dimension. Spider-Man teams up with Doctor Strange and his sidekick Wong to rescue Mary Jane and take back the Wand of Watoomb from Baron Mordo.

When Spider-Man discovers that his black costume is a living organism, he decides to use it to get back the Prometheum X. Meanwhile, Eddie Brock's lies eventually leads to his firing when Jameson realizes that he's been duped. Spider-Man eventually removes the symbiote after fighting the Shocker, only for it to find a new host, Eddie Brock.

Peter is on the brink of giving up the Spider-Man costume when he meets a mystic figure named Madame Web and his biggest fan, a little girl called Tyana. Meanwhile, Doctor Octopus returns and attacks Spider-Man with his new Octobot.

Spider-Man comes across an alien symbiote that attaches itself to him and forms a new black costume. Meanwhile, Eddie Brock accuses Spider-Man of stealing a valuable rock which was really stolen by the Rhino. Now Spider-Man faces a $1,000,000 bounty for his capture.

During Doctor Octopus' attack, Spider-Man loses his memory. Realizing the opportunity at hand, Doctor Octopus convinces Spider-Man to become his partner in crime. Luckily for Spidey, Tyana and a cabbie named Mousie witness the incident and hatch a plan to save their favorite super hero!

Spider-Man finds himself caught between Mariah Crawford, a doctor from Africa, and Kraven, a man who has stalked her all the way to America. An accomplished hunter, Kraven gained animal-like abilities when he ingested a cure to save his life, but the side effects are causing his behavior to be erratic and violent. Spider-Man works with Mariah Crawford to find a cure and save an innocent man and the people around him.