Thieves working fro Tombstone rob a building and try to escape via a helicopter on the roof. Spider-Man, back in his red-and-blue costume, goes after them. One manages to escape as Spider-Man defeats the others, and the wall crawler manages to swing onto the helicopter and take out the man. He helicopter goes into a tailspin but Spider-Man manages to catch it with his webbing before it can crash to the streets below. He leaves the robbers webbed up for the police, then goes to tell Tombstone to inform him their deal is off. After he leaves, a new black-clad figure enters: Venom. He wants to work for Tombstone, who tells him he needs to prove himself by eliminating Spider-Man. Venom is glad to oblige.
Peter goes to the hospital to visit Aunt May while he wonders about his responsibilities, toward others as Spider-Man, and toward himself and Aunt May. The next day he goes up to Flash at school and thanks him for giving him a hard time about turning on his friends. Flash tells him not to mention it… ever. Peter then apologizes to his friends, who invite him to help tow the giant balloon during the Thanksgiving Day parade the next day. He has to turn them down since he'll be bringing Aunt May home from the hospital. Gwen offers to be there for him. After she leaves, Mary Jane warns that Eddie Brock tried to hurt Peter by dating her. Peter calls Eddie to make up and Eddie says that they're fine and will be seeing more of each other soon.
After visiting Aunt May, Peter goes home to try and prepare a Thanksgiving meal so she doesn't have to. He messes it up and then considers the antidote he acquired from the Connors' lab. He wonders whether to take it or not so he can avoid his responsibilities. However, he's interrupted when Venom attacks him. Peter dons his costume and Venom comes after him and easily takes him down. However, the villain says that he'll leave Peter for later so that he will suffer, and warns that he knows all of Peter's secret.
Realizing Venom is going after his loved ones, Spider-Man heads for the hospital where Venom has sent Aunt May a bouquet and is watching from the window. Spider-Man attacks him and realizes that Eddie is the new Venom. Venom manages to escape and Peter figures he'll go after Mary Jane next.
The Midtown students, including Gwen and Mary Jane, are at the Thanksgiving Day parade. Flash is trying to put the moves on Mary Jane but she isn't having any. Spider-Man arrives and spots Gwen, webbed to a balloon and high above the ground. He tries to get to her but Venom is able to surprise him, since Peter's spider-sense doesn't work on the symbiote because it was bonded with him. The two fight while the webbing holding Gwen starts to fray. Mary Jane spots her and gets the others to help, while Peter lures Venom in and then tricks him into slashing open the balloon. It slowly descends as the webbing snaps, dropping Gwen toward the ground. Spider-Man manages to catch her but Venom knocks her loose. However, the students catch her using the hand of a balloon, breaking her fall.
Spider-Man and venom end up on a rooftop and Spider-Man realizes what he has to do. He surrenders… to the symbiote. He figures that it wants him back and offers no physical resistance. It pulls itself free from Eddie, who collapses from the shock. It absorbs Peter but this time his positive emotions of family and friends repel it. It falls off of him and tries to get back to Eddie, but Spider-Man wraps it in a bag and takes it to a building foundation where he dumps it in the setting concrete.
Peter returns home to find that Doc Bramwell has brought Aunt May home. Gwen and her father Captain Stacy arrive with Thanksgiving dinner, since Aunt May asked them to. They have dinner and talk about what their thankful for. Aunt May says that she is selling a cookbook, which should help with their debts.
Peter ends up cleaning up and considers the antidote… and then dumps it down the sink. As Gwen and her father leave, Peter thanks her and she starts to walk away. However, she reconsiders and gives him a romantic kiss before leaving. Peter is left to realize that the symbiote, which knew his thoughts, went after the girl he truly loved.
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