Five-level nested piloted neutral point clamped (5L-NPNPC) inverter is a new version of nested neutral point clamped multilevel topologies. In 5L-NPNPC, voltage fluctuations in the flying capacitors (FCs) and neutral point (NP) increase as the output frequency decrease, which is not desirable for the safe operation of the inverter. In this paper, a new model predictive control-based solution is proposed to tackle this problem. First, feasible combinations of space voltage vectors are determined through which the reference voltage of the inverter is synthesized. Then, a two-step optimization process is proposed to select the optimal switching states. The voltages of FCs and NP are the control objects in the first and second optimization steps, respectively. The proposed control scheme mitigates FCs and NP voltage fluctuations in the entire frequency range while keeping the switching frequency fixed. Also, the peak value of common-mode voltage (CMV) is limited to <italic xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">V<sub>dc</sub></i> /6. Furthermore, the proposed control scheme divides the optimization process into two steps, leading to a significant reduction in the computational burden of the processor. The mentioned achievements are important in medium-voltage (MV) motor drive applications. The simulation results and scaled-down experiments are provided to support the above claims.