The voice actors for The Amazing Spider-Man and Spider-Man 2099, Josh Keaton and Christopher Daniel Barnes respectively, were also the voice actors of Ultimate Spider-Man and Spider-Man Noir in the previous game Spider-Man: Shattered Dimensions (2010).
This game's story is written by Peter David, the co-creator of Spider-Man 2099, alongside directors Ramiro Bélanger and Gérard Lehiany.
J. Jonah Jameson mentions a Spider-Man musical during one of his rants about Spider-Man, to which Peter Parker responds; "I'd pay to see that". In real life a Spider-Man musical titled did open up on Broadway in 2011.
Peter Parker tells Miguel O'Hara during their initial conversation that he should play a video game if he wants a Spider-Man that will do what he says. This is ironic as he is in a video game.
This game was released a week after X-Men: Destiny (2011), another gamed licensed from Marvel Comics characters and released by Activision.