A heat pipe can be considered a highly effective thermal conduction device, which is especially desirable in heat transfer operations in order to ensure high energy efficiency. However, the operation of heat pipes comprises different heat and mass transfer phenomena, such phase change, heat conduction and convection, solid-liquid and vapor-liquid surface interactions, surface vaporization, and nucleate boiling. Therefore, modelling heat pipes is a highly complex task that demands detailed knowledge of the physical phenomena involved and choosing suitable theoretical models to obtain a good representation of the real nature of the heat and mass transfer processes. In this study, some models and parameters available in the commercial CFD software ANSYS Fluent for turbulence, density, phase change, and phase interfaces were examined to determine their influence on the prediction of the heat and mass transfer in a two-phased closed thermosyphon (TPCT). The numerical results show that using a turbulence viscous model is not necessary and that a variable density model improves the temperature distribution inside the TPCT. Furthermore, using high mass and energy transfer coefficients during condensation makes the vapor remain close to the saturation temperature. Finally, a sharp interphase model is strongly recommended for this type of process.