They are attacked by civilians infected by symbiotes. After a fight with Vulture, Spider-Man runs into many of Kingpin's henchman on top of the Daily Bugle. The duo joins forces with Moon Knight in order to stop Kingpin's illicit activities. After a brief battle, Black Cat reveals she is working for Kingpin.

He ends up confronting the Black Cat, who seems to be working with Kingpin. Outside the place of the meeting, Spider-Man discovers high-tech assassins on top of buildings after defeating them and leaving Cage to take care of the gangs. He manages to get them to accede to a meeting in a Harlem park. Spider-Man and Luke Cage hunt down the gang leaders of the city, the Roaring Sevens and Park Avenue gangs. After the encounter with Venom, an injured Mary Jane is sent to the hospital where she meets Luke Cage in the middle of a gang war. He retells his account of how his fight with Venom ended with a piece of the symbiote fastening to himself during a flashback to four days earlier. After finding Mary Jane with Luke Cage, Spider-Man is attacked by a mysterious figure.

At the same time, the city of New York is beset with symbiotes. The game opens with Spider-Man on a perquisition for Mary Jane Watson. 2.1 PS3, Xbox 360, PC and Wii storyline.

Spiderman web of shadows steam