Efficient actuation is crucial to obtaining optimal performance from nanoelectromechanical systems (NEMS). We employed epitaxial piezoelectric semiconductors to obtain efficient and fully integrated NEMS actuation, which is based on exploitation of the interaction between piezoelectric strain and built-in charge depletion. The underlying actuation mechanism in these depletion-mediated NEMS becomes important only for devices with dimensions approaching semiconductor depletion lengths. The induced actuation forces are controlled electrically, and resonant excitation approaching single-electron efficiency is demonstrated. The fundamental electromechanical coupling itself can be programmed by heterostructure band engineering, externally controllable charge depletion, and crystallographic orientation. These attributes are combined to realize a prototype, mechanically based, exclusive-or logic element.