Mosques are skin-load-dominated buildings; the temperature of their surrounding environment has a direct influence on their indoor thermal comfort and energy demands. So, it is thought that mosques' envelope design is a key element in optimizing their thermal and energy efficiency. Typically, perforated solar screens (PSS) are used as an outer skin to control solar radiation, reduce energy consumption, and improve visual appeal. The study aimed to use genetic algorithms (GAs) to identify the ideal perforated ratio of PSS that can reduce the annual solar irradiance in a hot, dry climate zone to its lowest values and consequently lessen thermal radiation and energy consumption. The analysis was performed on the men's prayer hall of El-Farouq Mosque in Cairo, Egypt, by applying an Islamic perforated screen to its southeast and southwest facades and roof. Galapagos optimization engine, via Grasshopper interface in Rhinoceros 3D software, was utilized to detect the optimal perforation ratio with the least annual solar irradiance. After that, an analysis was performed to measure the effect of the generated PSS on the thermal comfort and cooling loads of the hall during the hottest week of the year. The results showed that, compared to the current screen, a 0.25% PSS on the southeast and southwest facades and a 0.2% PSS on the roof could reduce the peak annual solar irradiance by 19%, improve thermal comfort measurements, and slightly lessen the cooling loads. Finally, a comparison was conducted between the thermal and energy performance of the current and the proposed PSS.