De Niro will play the reserved Paddy Connelly, who reluctantly agrees to fly to Sin City at the request of his friends. Douglas will play Billy Gerson, a lifelong bachelor, who has finally decided to take the plunge into marriage.
The famously intense De Niro may have made a name for himself in searing classics like "The Deer Hunter" and "Raging Bull," but he has increasingly been showing off his lighter side in comedies like "Meet the Parents." He was most recently seen playing a failed author in the drama "Being Flynn."
Douglas has also remained active despite a well-publicized battle with throat cancer, appearing in last winter's Steven Soderbergh thriller "Haywire" and in the upcoming HBO Liberace biopic "Behind the Candelabra."
This marks the first time the two Oscar-winners have starred opposite each other in a feature film.
Jon Turteltaub, who previously oversaw "National Treasure," will direct "Last Vegas."
Executive Vice President of Production Maria Faillace and Creative Executive Alex Ginno are overseeing the project for CBS Films.