Heterogeneous integration (HI) technologies present an important development in the pursuit of higher performance and reduced size, weight, power and cost of electronic systems (SWAP-C). HI systems, however, pose additional challenges for thermal management due to the disparate operating conditions of the devices. If the thermal coupling between devices can be reduced through a strategy of thermal isolation, then the SWAP-C of the accompanying thermal solution can also be reduced. This is in contrast to the alternative scenario of cooling the entire package to the maximum reliable temperature of the most sensitive devices. This isolation strategy must be implemented without a significant increase in device interconnect distances. A counter-intuitive approach is to seek packaging materials of low thermal conductivity – e.g. glass – and enhance them with arrays of metallic through-layer vias. This dissertation describes the first ever demonstration of integrating such via-enhanced interposers with microfluidic cooling, a thermal solution key to the high power applications for which HI was developed. Among the interposers tested, the best performing were shown to exhibit lower thermal coupling than bulk silicon in selective regions, validating their ability to provide thermal isolation. In the course of the study, the via-enhanced interposer is modeled as a thermal metamaterial with desirable, highly-anisotropic properties. Missing from the supporting literature is an accurate treatment of these interposers under such novel environments as microfluidic cooling. This dissertation identifies a new phenomenon, thermal microspreading, which governs how heat couples into a conductive via array from its surroundings. Both finite element analysis (FEA) and a new analytic solution of the associated boundary value problem (BVP) are used to develop a model for describing microspreading. This improves the ability to correctly predict the thermal behavior of via-enhanced interposers under diverse conditions.