An optimization strategy is proposed to improve the performance of a proton exchange membrane fuel cell (PEMFC) by using the theory of inventive problem solving (TRIZ) and game theory. TRIZ is widely used to provide solutions to the problems of systematic and innovative designs as it is based on the analysis of scientific and engineering aspects in patented technologies. Factors that improve and worsen the flow control of air and hydrogen are selected by TRIZ. The selected factors are assessed to establish quality optimization strategies, with game theory used to formulate the reward matrix from the negotiation between two parameters. A COMSOL simulation of quality gain and loss was performed using the measured data of inlet temperature, inlet pressure, and pressure drop, which were found to be important factors. The results showed that the outlet temperature, outlet pressure, and pressure drop were improved by 16.67, 78.8, and 11.73% by the control of the inlet temperature, inlet pressure, and flow of air and hydrogen, respectively. TRIZ with game theory was proved effective for obtaining an appropriate flow control strategy of a PEMFC, and provides an effective and easy way to design and manufacture a device when there are many factors and parameters to consider.