The movie stars Owen Wilson as a married Broadway director who falls for a prostitute-turned-actress and helps launch her career.
Aniston will play a therapist whose mother is in rehab for alcoholism, according to The Hollywood Reporter.
The Peter Bogdanovich film also stars Jason Schwartzman, Cybil Shepherd, Eugene Levy, Kathryn Hahn and Brie Lawson
Wes Anderson and Noah Baumbach are producing, while the script was co-written by Bogdanovich and Louise Stratten.
She's Funny That Way is due to begin shooting in New York City in June.
Aniston, who has also signed on to another comedy called Convention, previously starred opposite Wilson in 2008's Marley & Me.
Watch the trailer for Marley & Me below: