In this study, heat transfer in a heat sealing process was simulated using COMSOL Multiphysics software. Variations of thermal conductivity, specific heat, and density of polymers with temperature were measured in a wide temperature range. The temperature profile at the interface between two sealing films was measured using a fine thermocouple. Comparing experimental and simulation results indicated the high accuracy of the simulation and the significant role of considering thermal contact resistance as the boundary condition between the jaws and films. These results showed that the present simulation, for the first time, can successfully predict heat transfer and interface temperature in a heat sealing process without any fitting parameter. Moreover, the obtained results showed that the simulation can predict the effect of jaw temperature, sealing time, film thickness, and polymer crystallinity in a wide range of temperatures from below melting point to much higher temperatures than the melting point of the sealant.