One of the key challenges in the thermal management of electronic packages are interfaces, such as those between the chip and heat spreader and the interface between a heat spreader and heat sink or cold plate. Typically, thermal interfaces are filled with materials such as thermal adhesives and greases. Interface materials reduce the contact resistance between the mating heat generating and heat sinking units by filling voids and grooves created by the nonsmooth surface topography of the mating surfaces, thus improving surface contact and the conduction of heat across the interface. However, micron and submicron voids and delaminations still exist at the interface between the interface material and the surfaces of the heat spreader and semiconductor device. In addition, a thermal interface material (TIM) may form a filler-depleted and resin-rich region at the interfaces. These defects, though at a small length scale, can significantly deteriorate the heat dissipation ability of a system consisting of a TIM between a heat generating surface and a heat dissipating surface. The characterization of a freestanding sample of TIM does not provide a complete understanding of its heat transfer, mechanical, and interfacial behavior. However, system-level characterization of a TIM system, which includes its freestanding behavior and its interfacial behavior, provides a more accurate understanding. While, measurement of system-level thermal resistance provides an accurate representation of the system performance of a TIM, it does not provide information regarding the physical behavior of the TIM at the interfaces. This knowledge is valuable in engineering interface materials and in developing assembly process parameters for enhanced system-level thermal performance. Characterization of an interface material between a silicon device and a metal heat spreader can be accomplished via several techniques. In this research, high-magnification radiography with computed tomography, acoustic microscopy, and scanning electron microscopy were used to characterize various TIM systems. The results of these characterization studies are presented in this paper. System-level thermal performance results are compared to physical characterization results.