There has been a theoretical investigation for energy, exergy, and economic evaluation of thermal regulation of PV panels via an innovative hybrid cooling system of flat heat pipes (HPs) coupled with phase change material (PCM). PV panel dissipates its heat through the HP evaporator while the HP condenser is cooled by PCM. The cooling system performance is investigated for different PCM quantities and types (RT42, RT35HC, and SP31) for summer and (RT21, RT18HC, and SP15-gel) for winter conditions in Egypt. A thorough study and analysis have been conducted for the impact of the cooling system on PV panel's temperature, electric efficiency, output power, PCM energy storage, and system efficiency. The results show that compared with conventional PV, the best PCM type for PV performance in summer is SP31 of 3 cm thickness, which achieves a maximum PV temperature reduction of 20.6 °C with a maximum improvement in PV electric efficiency of 11.5%. SP15-gel of thickness 2.5 cm is the best PCM for winter conditions, achieving 14.1 °C temperature reduction with 7.2% enhancement in PV electric efficiency. The exergy efficiency of the PV panel is higher than in PCM, where it rises as the phase change temperature of the PCM increases. PV maximum average daily exergy efficiency is 13.4% for SP15-gel, compared with 12.71% for conventional PV in winter, while SP31 achieved 12.25%, 1% higher than reference PV in summer. PCM's maximum average daily exergy efficiency is 0.69% and 0.7% for RT42 and RT21 in summer and winter, respectively. The minimum payback period for conventional PV is about 18.01 years, while it is approximately 13.39 years for PV with HP and PCM. The studied cooling system at different PCMs proves its capability to enhance the PV performance with higher energy and exergy efficiencies and lower cost and store the excess heat inside the PCM.