McCarthy has co-written the raunchy script with husband Ben Falcone, who will direct the New Line film, said the Hollywood Reporter.
The story centers on a woman who is laid off from her job at a fast food restaurant, discovers her husband is having an affair and decides to go on a road trip with her alcoholic, foul-mouthed, diabetic grandmother.
Shirley MacLaine was previously in talks to star as the grandmother, but the deal never happened.
Kathy Bates will play the grandmother's lesbian friend who saves the duo from some bad spots.