Piezoelectric energy harvesters (PEHs) have drawn considerable attention due to their unique ability to convert ambient mechanical energy to electrical energy. These devices are widely implemented in numerous applications such as wearable technology, structural health monitoring, and renewable energy systems. In this work, a novel approach that seamlessly integrates arbitrary metastructures into the substrate layer of cantilever beam‐based PEHs is presented. The corresponding performance of each PEH design is evaluated via an experimentally validated finite element model. This is the first systematic study to explore 3D metastructures with various unit cell configurations, unit cell numbers, and porosity levels. Compared with the existing PEH designs, implementation of a 3D auxetic metastructure with 85% porosity single unit cell design can demonstrate a substantial enhancement in output power, reaching 48.16 mW, and a high normalized power density (NPD) of 2.1131 µW mm−3 g−2 Hz−1. Results show that there are competing requirements for improving the performance of PEHs. On one hand, low metastructure stiffness is preferred to achieve high power output at low resonant frequency. On the other hand, metastructures designs with low stiffness may induce excessive distortion in the substrate layer, leading to mechanical energy loss. This deformation mechanism adversely affects the mechanical to electrical energy conversion efficiency. Detailed guidelines for designing and manufacturing high‐performance PEHs are discussed in this work.