Plate heat exchangers (PHEs) play a vital role in the processes of heat transfer and energy conservation. To find the best combined optimization result using the criteria of PHE heat transfer and energy conservation, a multi-objective genetic algorithm optimization (MOGAO) targeting the minimum -JF factor and entropy generation was carried out on the PHE, and 100 optimization results were comprehensively assessed by a quantitative energy efficiency index (EEI). Finally, the comparisons of JF factor, entropy generation per mass flow rate (EGPMFR), and EEI between improved scheme 6 (IS6) and original scheme were numerically discussed under the same configuration. It is found that the deviation between experimental data and simulation results could enable further analyses within the specific range. Under the inlet velocity of 0.6 m/s, the JF factor, EGPMFR, and EEI of IS6 increase by 12.20%, 19.42%, and 8.82%, respectively. This work may somehow offer a reference for the PHE comprehensive optimization.