Co-starring Alicia Silverstone and Krysten Ritter, the movie is described as a "modern-day tale of two young, beautiful female vampires living the good nightlife in New York until love enters the picture and each has to make a choice that will jeopardize their immortality."
Weaver will play the role of Ciccerus, a bloodthirsty "stem" vampire who has created a dynasty, the film's producers said.
Her film credits include "Ghostbusters," "Aliens," "Gorillas in the Mist," "The Village," "Baby Mama" and "Avatar."
"Vamps" is set to start production in May.
It is being produced by Red Hour Films, Lucky Monkey Pictures' Lauren Versel and Molly Hassell. Executive producers include Julie Kroll and Maria Teresa Arida.
Heckerling has directed the hits "Fast Times at Ridgemont High," "Look Who's Talking" and "Clueless."