Abstract Piezoelectric nanostructures can transduce mechanical energy into electrical energy for powering implantable microsystems for in-vivo biomedical applications (smart systems for drug delivery, μTAS, microsensors for diagnostic and therapeutic applications …) and sensors networks for high-density, low cost environment control. Zinc oxide nanowires and microwires have been recently used to convert vibrations into electrical energy. Here, we explain some previously reported experimental results and provide insight for the design of high-efficiency piezoelectric nanogenerators. Additionally, since the dimension and position of the electrical contacts, as well as the direction of the input force, can be very important, we define and systematically compare the most important configurations for 2-contacts piezoelectric nanowires; finally, we suggest that piezoelectric nanowalls can effectively increase the output currents. Our results are consistently confirmed by FEM simulations and can be a guidance for the design of high-efficiency energy harvesting devices and for the development of novel fabrication procedures.