James Horan and David Kaye replaced Hugh Laurie and Will Arnett as the voices of Dr. Cockroach and The Missing Link respectively.
Susan and Insectosaurus don't appear in the film.
B.O.B. is seen as an infant in this film, but in Monsters vs. Aliens (2009), he is already in his adult size when he was born.
When B.O.B. takes all the plush toys, one of them is Alex from Madagascar (2005).
Susan and Insectosaurus appear, but only in footage from Monsters vs. Aliens: Mutant Pumpkins from Outer Space (2009).