In this study, the performance of hybrid nanofluids in a flat plate solar collector was analysed based on various parameters such as entropy generation, exergy efficiency, heat transfer enhancement, pumping power, and pressure drop. Five different base fluids were used, including water, ethylene glycol, methanol, radiator coolant, and engine oil, to make five types of hybrids nanofluids containing suspended CuO and MWCNT nanoparticles. The nanofluids were evaluated at nanoparticle volume fractions ranging from 1% to 3% and flow rates of 1 to 3.5 L/min. The analytical results revealed that the CuO-MWCNT/water nanofluid performed the best in reducing entropy generation at both volume fractions and volume flow rate when compared to the other nanofluids studied. Although CuO-MWCNT/methanol showed better heat transfer coefficients than CuO-MWCNT/water, it generated more entropy and had lower exergy efficiency. The CuO-MWCNT/water nanofluid not only had higher exergy efficiency and thermal performance but also showed promising results in reducing entropy generation.