The combination of 3D processing technologies, low power circuits and new materials integration makes it conceivable to build autonomous integrated systems, which would harvest their energy from the environment. In this paper, we focus on mechanical energy harvesting and discuss its scaling prospects toward the use of piezoelectric nanostructures, able to be integrated in a CMOS environment. It is shown that direct scaling of present MEMS-based methodologies would be beneficial for high-frequency applications only. For the range of applications which is presently foreseen, a different approach is needed, based on energy harvesting from direct real-time deformation instead of energy harvesting from vibration modes at or close to resonance. We discuss the prospects of such an approach based on simple scaling rules