Skylights are an efficient means of daylighting in exhibition spaces, but their design presents significant challenges. Considering that daylight utilization profoundly impacts both the visual and thermal environments while affecting energy consumption, the early application of multi-objective optimization strategies becomes imperative. However, many optimization studies provide numerical references only, without delving into the characteristics of opening distribution. This study introduces an optimized exploration approach for openings based on grid subdivision and material parameter selection, targeting Useful Daylight Illuminance (UDI), Energy Use Intensity (EUI), and Predicted Percentage of Dissatisfied (PPD). Simulations and optimizations were performed using Honeybee and Octopus, focusing on the optimal configurations of four typical skylights in Fukuoka, Japan’s climate. The results demonstrate that this novel optimization approach improves metrics for each case and challenges traditional perceptions of daylight systems. Flexible and diverse opening configurations, formed through irregular layouts and material combinations, help achieve more ideal holistic environmental effects under different climatic conditions. Thus, we should provide these research findings as design guidelines for similar scenarios.