In this work, a two-dimensional pore network model is developed to study the heat and mass transfer inside a capillary porous wick with opposite replenishment in the dry-out regime. The mass flow rate in each throat of the pore network is computed according to the Hagen–Poiseuille law, and the heat flux is calculated based on Fourier’s law with an effective local thermal conductivity. By coupling the heat and the mass transfer, a numerical method is devised to determine the evolution of the liquid–vapor interface. The model is verified by comparing the effective heat transfer coefficient versus heat load with experimental observations. For increasing heat load, an inflation/deflation of the vapor pocket is observed. The influences of microstructural properties on the vapor pocket pattern and on the effective heat transfer coefficient are discussed: A porous wick with a non-uniform or bimodal pore size distribution results in a larger heat transfer coefficient compared to a porous wick with a uniform pore size distribution. The heat and mass transfer efficiency of a porous wick comprised of two connected regions of small and large pores is also examined. The simulation results indicate that the introduction of a coarse layer with a suitable thickness strongly enhances the heat transfer coefficient.