Hydrogen (H2) has become an important energy vector for mitigating the effects of climate change since it can be obtained from renewable sources and can be fed to fuel cells for producing power. Bioethanol can become a green H2 source via Ethanol Steam Reforming (ESR) but several variables influence the power production in the fuel cell. Herein, we explored and optimized the main variables that affect this power production. The process includes biomass fermentation, bioethanol purification, H2 production via ESR, syngas cleaning by a CO-removal reactor, and power production in a high temperature proton exchange membrane fuel cell (HT-PEMFC). Among the explored variables, the steam-to-ethanol molar ratio (S/E) employed in the ESR has the strongest influence on power production, process efficiency, and energy consumption. This effect is followed by other variables such as the inlet ethanol concentration and the ESR temperature. Although the CO-removal reactor did not show a significant effect on power production, it is key to increase the voltage on the fuel cell and consequently the power production. Optimization was carried out by the response surface methodology (RSM) and showed a maximum power of 0.07 kWh kg−1 of bioethanol with an efficiency of 17%, when ESR temperature is 700 °C. These values can be reached from different bioethanol sources as the S/E and CO-removal temperature are changed accordingly with the inlet ethanol concentration. Because there is a linear correlation between S/E and ethanol concentration, it is possible to select a proper S/E and CO-removal temperature to maximize the power generation in the HT-PEMFC via ESR. This study serves as a starting point to diversify the sources for producing H2 and moving towards a H2-economy.