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Back to School is a mission in Marvel's Spider-Man. Immediately after Spider-Man disarms the bombs left in the city during the What's in the Box? mission, Mary Jane Watson phones him and shares a picture of Isaac Delaney she uncovered; the only problem is she does not know which person he is. In order to figure it out, Peter Parker has to go to an Empire State University Halloween party.

Players are free to search the party-goers as Spider-Man since everyone is in costume. Delaney is dressed as The Lizard, dancing on the dance floor. Before he can talk to him, a student dressed as the Rhino interrupts, keeping him occupied with some of the Inner Demons take Delaney away. The student is easy to deal with (press Square repeatedly), and then players are free to follow into the Science Center.

Spider-Man watches from above as they escort Delaney through the hall, but must intervene when one of the students decides to ignore the Demons and walk out. A Demon puts a gun to his head, and players must rapidly target it in order to save the student. On the floor, players must face off against the remainder of the Demons. Once dealt with, players need to enter the vent above the laboratory to gain access.

Within the vent, players need to use their Electric Web to knock out the lighting before entering the room. As long as Spider-Man remains in the shadows, he seems to retain an advantage in the fight. When the Demons are dealt with, he learns Delaney has been taken further into the building. At this point, players exit the room via a window, to track Delaney from the outside as he is escorted down the halls. Another vent allows entry to the room that the doctor is taken into, where he is met by Martin Li.

Li turns into Mister Negative for the first time in front of Spider-Man, who tries to intervene. Li manages to incapacitate him with a massive blast, gaining a name from Delaney as to whom he was working with at Oscorp: Morgan Michaels. With this information in-hand, Li leaves with his Demons, leaving a "negative" possessed Delaney to shoot himself in the head. Players are left to deal with the remaining Demons.

Chasing Li outside only results in party-goers influenced by his negative power, and players must battle them as well. Spider-Man then warns Yuri that Michaels is in trouble.

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