Thermal energy storage using phase change materials (PCMs) is a promising technology for improving the thermal performance of buildings and reducing their energy consumption. However, the effectiveness of passive PCMs in buildings depends on their optimal design regarding the building typology and typical climate conditions. Within this context, the present contribution introduces a novel multiobjective computational method to optimize the thermophysical properties of cementitious building panels enhanced with a microencapsulated PCM (MPCM). To achieve this, a parametric model for PCM-based cementitious composites is developed in EnergyPlus, considering as design variables the melting temperature of PCMs and the thickness and thermal conductivity of the panel. A multiobjective genetic algorithm is dynamically coupled with the building energy model to find the best trade-off between annual heating and cooling loads. The optimization results obtained for a case study building in Sofia (Bulgaria-EU) reveal that the annual heating and cooling loads have contradictory performances regarding the thermophysical properties studied. A thick MPCM-enhanced panel with a melting temperature of 22 °C is needed to reduce the heating loads, while a thin panel with a melting temperature of 27 °C is required to mitigate the cooling loads. Using these designs, the annual heating and cooling loads decrease by 23% and 3%, respectively. Moreover, up to 12.4% cooling load reduction is reached if the thermal conductivity of the panels is increased. Therefore, it is also concluded that the thermal conductivity of the cement-based panels can significantly influence the effectiveness of MPCMs in buildings.