Kirigami and auxetic topologies are combined to design an innovative metamaterial-based substrate (MetaSub) for piezoelectric energy harvesters. The proposed MetaSub piezoelectric energy harvester (MPEH) contains both advantageous metamaterial properties of negative Poisson’s ratio capability and enhanced planar stretchability. A computational parametric analysis is conducted to develop the optimum design for the MPEH to trap the maximum elastic energy. A finite element analysis (FEA) is employed to analytically and numerically validate the simulation model of the MPEH. Accordingly, two experimental results of conventional and auxetic strain energy harvesters are used to evaluate the power enhancement of the MPEH. The FEA results demonstrate the average power gained by the MPEH at a low level of frequency and strain excitation (10 Hz and 150 peak-to-peak) is 165 W which easily satisfies the minimum electric power amount required as a sensor node for self-powered wireless sensor networks. The harvested power output of the MPEH is 19.2 times more than power output produced by an equivalent conventional harvester with a plain substrate (8.6 W). The performance of the MPEH is investigated at different combinations of both low and high excitation frequencies. The creative design of the MetaSub can significantly improve the productivity of strain-induced devices whose efficiency is dependent on their deformation performance such as vibration energy harvesters, wearable sensors, flexible actuators, and micro electromechanical applications.