Mitigation of 'hot spots' in microelectromechanical systems (MEMS) employing in situ microchannel systems requires a comprehensive picture of the maldistribution of the working fluid and uniformity of cooling within the same. In this paper, detailed simulations employing parallel microchannel systems with specialized manifold-channel configurations, i.e., U, I, and Z, have been performed. Eulerian-Lagrangian discrete phase model (DPM) and effective property model with water and alumina-water nanofluid as working fluids have been employed. The distributions of the dispersed particulate phase and continuous phase have been observed to be, in general, different from the flow distribution, and this has been found to be strongly dependent on the flow configuration. Accordingly, detailed discussions on the mechanisms governing such particle distribution patterns have been proposed. Particle maldistribution has been conclusively shown to be influenced by various migration and diffusive phenomena, such as Stokesian drag, Brownian motion, thermophoretic drift, and so on. To understand the uniformity of cooling within the device, which is of importance in real-time scenario, an appropriate figure of merit has been proposed. It has been observed that uniformity of cooling improved using nanofluid as working fluid as well as enhanced relative cooling in hot zones, providing evidence of the 'smart' nature of such dispersions. To further quantify this smart effect, real-time mimicking hot-spot scenarios have been computationally probed with nanofluid as the coolant. A silicon-based microchip emitting nonuniform heat flux (gathered from real-time monitoring of an Intel Core i7-4770 3.40-GHz quad-core processor) under various processor load conditions has been studied, and the evidence of enhanced cooling of hot spots has been obtained from DPM analysis. This paper sheds insight on-the behavior of nonhomogeneous dispersions in complex flow domains and the caliber of nanofluids in cooling MEMS more uniformly and 'smarter' than base fluids. © 2011-2012 IEEE.