Barrymore, 38, and Sandler, 46, will play the leads in Frank Coraci directed "Blended", reported Ace Showbiz.
The couple are stuck at the same resort with their respective children from previous marriages.
Production for the upcoming movie is expected to begin sometime in May.
It will mark the third time Barrymore and Sander star opposite each other.
They first teamed up in 1998's Coraci-directed romcom "The Wedding Singer" and became an on-screen couple once again in 2004's "50 First Dates".