Thermal management is considered as a bottleneck for the development of next generation micro/nano-electronics with high heat dissipation rates. When component sizes decrease to nanoscales, increase in surface to volume ratio leads the interfacial thermal resistance (ITR) to dominate the heat transfer behavior. The current study focuses on characterizing ITR at molecular level and exploring smart thermal management concepts for nano-scale systems. In sequence, the effect of solid thickness on ITR was investigated such that the altered phonon spectrum inside the solid domain creating the size dependency on thermal conductivity was also found to create a size dependency in ITR. Next, an active and local manipulation of heat transfer between water and various solids by an applied uniform and/or non-uniform electric field was examined. When the water molecules underwent electric field induced orientation polarization and liquid dielectrophoresis (LDEP), a substantial increase in heat transfer was developed due to the decrease in ITR and increment in thermal conductivity. Finally, an interface-localized heat transfer control technique was proposed, where interdigitated electrodes (IDEs) were embedded into the heat dissipating surface. IDEs created an electric field gradient exclusively near the electrode surface which resulted in LDEP forces on the water dipoles at near surface region enhancing solid/liquid interface energy and almost eliminating the ITR. We developed semi-empirical and theoretical relations to describe ITR variation by the electric field, which will be important for thermal management of current and future technologies.