Addressing the global energy demand and climate change mitigation requires novel strategies for renewable energy utilization. Photovoltaic (PV) systems harness solar power and are critical contributors to this clean energy transition. However, stand-alone PV systems capture only a fraction of the incident solar energy, thus limiting their overall energy conversion efficiency. To overcome this limitation, this study investigates the performance of integrated photovoltaic/thermal (PV/Thermal) systems that generate electricity and leverage solar energy for thermal applications. This research compares a stand-alone PV panel and six other innovative PV/Thermal configurations. Each configuration exhibits a unique serpentine-based four-compartment thermal absorber design. A comprehensive energy, exergy, and CO2 emission reduction evaluation combined with the Response Surface Methodology (RSM) technique is assessed in this study. The RSM technique generates regression models for all proposed PV/Thermal designs that can predict the output response as a function of the weather data. Finally, the Energy Payback Time is assessed for both systems to evaluate their financial feasibility. The results reveal that the uncooled PV system shows the shortest EPBT, while the PV/Thermal system offers additional benefits through combined electricity and thermal energy generation. Regarding CO2 emissions and mitigation over their lifespan, the PV/Thermal system could reduce the annual CO2 emissions by an average of 6.42 tons per year.