The current limitations of air-cooled proton exchange membrane fuel cells (AC-PEMFCs) in water and heat management remain a major obstacle to their commercialization. A 90 cm2 full-size AC-PEMFC multi-physical field-coupled numerical model was constructed; isothermal and non-isothermal calculations were performed to explore the effects of univariate and multivariate variables on cell performance, respectively. The isothermal results indicate that lower temperature is beneficial to increase the humidity of MEA, and distribution uniformity at lower stoichiometric ratios and lower temperatures is better. The correlation between current density distribution and temperature, water content, and concentration distribution shows that the performance of AC-PEMFCs is influenced by multiple factors. Notably, under high current operation, the large heat generation may lead to high local temperature and performance decline, especially in the under-channel region with drier MEA. The higher stoichiometric ratio can enhance heat dissipation, improve the uniformity of current density, and increase power density. Optimal fuel cell performance is achieved with a stoichiometric ratio of 300, balancing the mixed influence of multiple factors.