Goldberg will guest star as Poundcakes, Hamm will play Iron Man, Fillion will play Wonder Man and Hader will play Angar the Screamer and The Leader, Hulu announced Saturday.
The animated series is set to debut on Hulu May 21.
"The megalomaniacal supervillain M.O.D.O.K. (Patton Oswalt) has long pursued his dream of one day conquering the world. But after years of setbacks and failures fighting the Earth's mightiest heroes, M.O.D.O.K. has run his evil organization A.I.M. into the ground," a synopsis for the show said. "Ousted as A.I.M.'s leader, while also dealing with his crumbling marriage and family life, the Mental Organism Designed Only for Killing is set to confront his greatest challenge yet!"
The vocal ensemble will also include Melissa Fumero, Aimee Garcia, Ben Schwartz, Wendi McLendon-Covey, Beck Bennett, Jon Daly and Sam Richardson.
Marvel's M.O.D.O.K. was created and written by executive producers Oswalt and Jordan Blum.