Dr. Otto Octavius is an egomaniacal scientist that was conducing an experiment, but it failed in an accident which turned him on villain Dr. Octopus (a.k.a. Doc Ock). Now he seeks revenge on the one he holds responsible for humiliating him: Spider-Man.

The N-Gage version of Spider-Man 2 is a 2D platformer, with some 3D races against time between the 2D stages. In the 3D races Spider-Man needs to move higher or lower between buildings to avoid obstacles. The 2D levels are more traditional: climbing walls and ceilings, slinging web at opponents, taking pictures for the Daily Bugle newspaper, using spider sense to reveal secrets etc. The events are loosely based on the story of the Spider-Man 2 movie. The game offers fifteen 2D levels, five 3D levels, some Spider-Man comics' classical villains as bosses (like The Lizard, Rhino, and Doc Ock) and a scoreboard on N-Gage Arena.