Phase Change Materials have been acknowledged for their potential to be used as passive strategy for improving energy efficiency and occupants' thermal comfort in buildings. However, their performance still needs to be enhanced to have them effectively used. In this view, this study investigates the potential improvement of PCMs performance for passive cooling application by efficient natural ventilation in residential building stock. Therefore, coupled dynamic simulation and optimization analysis is performed to explore the optimum melting temperature of PCM integrated in the external building envelope to minimize cooling loads in different Italian climate zones. Moreover, various natural ventilation control strategies are implemented to assess their influence on the process of PCM charge-discharge cycle. Results show that PCM inclusion in the building envelope provides significant cooling savings, up to about 300 kWh/year in mild climates. Furthermore, both night and temperature controlled natural ventilation are able to enhance the efficiency of PCMs thermal energy storage charge-discharge cycle. However, the optimum performance is obtained by coupling PCMs with natural ventilation controlled by indoor/outdoor temperature difference in all considered climate contexts. Accordingly, considerable building cooling energy need reduction is achievable through the optimum combination of PCMs and natural ventilation control, especially in milder climates.