This article documents some of the factors that influence the heat transfer through polysynthetic thermal compounds at the central processing unit ( CPU)/heat sink interface. First, special attention is paid to assessing the effect of mechanical and thermal properties of the contacting bodies, applied contact pressures, and surface roughness characteristics, as well as the use of different thermal interface materials on the maximum temperature experienced by the CPU. Second, it can be appreciated that good wetting of the mating surfaces and the retention of asperity micro-contacts can become critical elements in effectively removing the heat generated by the CPU. This study uses the Holman model for calculating the heat transfer, indicating the role of thermal contact resistance. The mathematical results clearly indicate that any strain in the interface material leads to a change in thermal contact resistance, with an effect on CPU overheating. Experimentally obtained images with an atomic force microscope clearly revealed that eliminating micro-gaps using thermal interface materials can facilitate the heat transfer by significantly lowering the thermal contact resistance of the CPU/heat sink assembly. This effect is amplified by the plastic deformation of micro-contacts due to high contact pressures and lower micro-hardness levels.