Aradan ikl yıl geçmiştir. Peter Parker, yeni zorluklarla mücadele etmek ve süper kahraman Örümcek adam ile üniversite öğrencisi kimliği arasındaki dengeyi korumak zorundadır. Sakladığı sır yüzünden acı çeken Peter'ın, en önem verdiği insanlar onun yüzünden farkında olmadıkları bir tehlikenin içindedir. Ç:ünkü Peter güçlü ve çok kollu ve kötü yürekli Dr. Octopus (Ahtapot) ile karşı karşıyadır.

Peter Parker, a.k.a. Spider-Man, is desperately trying to balance his dual identities. He can't keep up at college, pay his rent, or seem to make amends with his estranged best friend Harry and his beloved Mary Jane is more skeptical than ever. Peter begins to notice that he's losing some of his powers and wonders if the cost of being a superhero isn't too high. Meanwhile Peter's idol, the renowned scientist Otto Octavius, has turned into a maniacal cyborg after a failed science experiment. Peter realizes he must decide between the ordinary life he so desires and the responsibilities of retaining his secret identity to stop "Doc Ock" and save New York City from destruction.