A supposedly reformed Dr.
Otto Octavius is holding a scientific demonstration at the Science Expo 2000, but is interrupted when an impostor
Spider-Man attacks the crew and steals his equipment.
Eddie Brock tries to take pictures for the
Daily Bugle, but the impostor shatters his camera. In a rage, the
Venom symbiote resurfaces inside Brock, and he vows vengeance against Spider-Man. Meanwhile, the real Spider-Man, who witnessed the incident as Peter Parker, is held responsible for the theft and the police ensue a manhunt for him. Elsewhere, two unseen figures release dense amounts of mysterious fog from their hidden base into the city which quickly covers the streets. After meeting with
Black Cat and foiling a bank robbery by the Jade Syndicate, Spider-Man is forced to save
J. Jonah Jameson from
Scorpion at the
Daily Bugle. He defeats Scorpion only for an ungrateful Jameson to call the police on him. While trying to escape, Spider-Man encounters
Daredevil who promises to spread the word about Spider-Man's innocence. After evading a police helicopter, Spider-Man reunites with Black Cat who informs him of two new problems:
Rhino is attacking a power plant and Venom has kidnapped his wife
Mary Jane Parker to lure out Spider-Man. Choosing to deal with Rhino first, Spider-Man and Black Cat defeat him and leave him for the police, but Black Cat gets badly wounded during the fight and is kidnapped by unknown assailants posing as
paramedics. After encouragement from
Human Torch, Spider-Man sets out to find Venom only for Venom to instead find Spider-Man and goad him, leading to a chase throughout the city and eventually into Venom's hideout in the sewers. During his pursuit, Spider-Man encounters the
Lizard who was imprisoned by Venom after taking control of his
Lizard Men (who attacked Spider-Man at various points during the chase). The Lizard points Spider-Man to Venom's lair where the former rescues Mary Jane and defeats Venom. To make amends with Spider-Man after learning he was framed, Venom offers to assist him in finding the culprit to which Spider-Man begrudgingly agrees. The two head to the
Daily Bugle to search through Jameson's files for answers. During the search, Venom senses
Carnage's presence nearby and leaves to find him. Left to investigate on his own, Spider-Man discovers an infestation of
Symbiotes in the building and clears them out before encountering the impostor Spider-Man, who revealed to be
Mysterio in disguise. After defeating him, Spider-Man learns Mysterio was hired to keep Spider-Man distracted while his employer infests New York with Symbiotes and that the fog over the city will act as a beacon for the symbiotes, preparing the citizens for
symbiosis. On his way to Warehouse 65 where the hideout of Mysterio's employer is located, Spider-Man encounters
Punisher, whom he convinces about his innocence. In turn, Punisher offers Spider-Man help with infiltrating the warehouse. Not looking to raise the amount of casualties, Spider-Man declines. Spider-Man discovers an entrance to a massive undersea base inside the warehouse and proceeds to investigate, quickly coming across a symbiote manufacturing operation and an imprisoned Black Cat. After disrupting the operation and rescuing Black Cat, Spider-Man finally confronts her kidnappers and the masterminds behind the Symbiote invasion: Dr. Octavius and Carnage. Taking up his Doctor Octopus persona once again, Octavius explains that he faked his reform and that, with the help of Carnage (who donated his Carnage symbiote to be cloned), he hopes to create a new world dominated by symbiotes under his rule. Later, Venom appears and takes on Carnage while Spider-Man fights Doctor Octopus. After both Doctor Octopus and Venom are defeated, Spider-Man fights Carnage and defeats him by sustaining him into a sonic bubble. Following his defeat, the Carnage symbiote separates from
Cletus Kasady and fuses with Doctor Octopus, creating "Monster-Ock". Unable to perform an effective battle, Spider-Man is chased by the monstrosity out of the self-destructing base until it is caught in one of the explosions which removes the symbiote from Doctor Octopus's body. As the Carnage symbiote slithers back into the burning base, Spider-Man carries the unconscious Doctor Octopus to the surface where they are salvaged by
Captain America, Black Cat, and Venom in an aircraft. Sometime later, Spider-Man is playing cards with Captain America, Daredevil, and the Punisher, while Black Cat and the Human Torch are dancing. In prison, Doctor Octopus' cellmates—Mysterio, Rhino, Scorpion, and a Jade Syndicate thug—are also playing cards. Mysterio mentions to Rhino, Scorpion, and the Jade Syndicate thug that nobody can control the Symbiotes. When Rhino mistakenly thinks he got a bingo, he accidentally sends the Jade Syndicate thug's head through the roof. Annoyed and despondent, Doctor Octopus bangs his head against the cell bars. ==Development==