Liquid water saturation of pores in the gas diffusion layer (GDL) and the catalyst layer (CL) of polymer electrolyte membrane fuel cells (PEMFC) hinders the transport of the reactant gases, leading to inhomogeneous current density distribution, reduced overall cell performance, and accelerated material degradation. This effect restricts the PEMFC operation, specifically at high current densities. In this study, the simulation results illustrate how the interplay of wettability and pore sizes influences the water distribution within the CL, microporous layer (MPL) of the GDL, and specifically their interface. The liquid water distribution within the porous material is studied employing a voxel-based Monte Carlo (MC) model reflecting the effect of local thermodynamic boundary conditions and inner surface characteristics. Real material structures obtained with a focused ion beam scanning electron microscope (FIB-SEM) are employed. Local temperature and relative humidity values required as inputs are obtained from sophisticated computational fluid dynamics (CFD) simulations comprising all relevant effects, including the electrochemical reactions. The results show that avoiding drastic changes in wettability at the CL-MPL interface can help to mitigate the possible detrimental water accumulations. Further developing and exploiting this study will contribute to facilitate the systematic material development for better PEMFC performance and durability.