Spider-Man's new costume is made from nano technology from the lab of Reed Richards, a.k.a. Mr. Fantastic (the leader of the super-hero team the Fantastic Four).
Venom and Carnage have morphing powers which turns their whole body into liquid texture. Spider-Man mentions they never had such powers before.
S.H.I.E.L.D. agent Nick Fury makes a cameo appearance.
One of Spider-Man's classic villains from the comics, Doctor Octopus appears on Peter and Mary Jane's television during a news segment on Spider-Man. Dr. Octopus' only line of dialogue is a faint grunt when Spider-Man punches him in their brief fight.
Jennifer Hale, who does the voice of Mary Jane Watson on this series, also provided the voice of Felicia Hardy/Black Cat on the completely unrelated Spider-Man: The Animated Series (1994) animated series that aired on FOX.