The Montreal Protocol’s phase-out of R134a led to adopting R1234yf in automotive heat pump systems. However, emerging PFAS (per- and poly-fluoroalkyl substances) regulations now necessitate transitioning to natural refrigerants. In addition, R290 has an advantage in a secondary-loop heat pump system for waste heat usage due to its higher latent heat. This study evaluates R290 (propane) as a drop-in replacement for R1234yf, focusing on minimizing system redesign. It is important to determine the optimal charge of the system without a receiver. Volumetric flow rate-based and cooling capacity-based methods were applied to determine the initial charge of R290. Numerical simulations performed under heating and cooling modes revealed that R290 failed to achieve subcooling at the condenser outlet. Partial condensation is due to its high latent heat. Increasing heat exchanger capacity from 6 to 10 kW did not resolve this limitation. However, reducing the refrigerant charge by 0.6 kg enabled complete condensation of R290 in both operating modes without system redesign. These findings highlight refrigerant charge optimization, rather than hardware redesign, as a critical factor for the interchangeability of R290. The results demonstrate that minor adjustments to operational parameters can align natural refrigerant performance with regulatory and efficiency requirements. This approach offers a cost-effective pathway for automotive industries to comply with PFAS restrictions while maintaining thermal system functionality. The study underscores the potential of R290 as a sustainable alternative, providing actionable insights for minimizing retrofit complexities in evolving regulatory landscapes..