A multi-objective optimization strategy, based on stacked neural network–genetic algorithm (SNN–GA) hybrid approach, was applied to study the C/PBI content on a high temperature PEMFC performance. The operating conditions of PEMFC were correlated with power density and electrochemical active surface area for electrodes. The structure of the stack was determined in an optimal form related to the contribution of individual neural networks, after applying an interpolation based procedure. Multi-objective optimization using SNN as model and GA as solving procedure provides optimal working conditions which lead to a high PEMFC performance. Simulation results were in agreement with experimental data, both for model validation and system optimization (the C/PBI content in the range of 17–21%).