Silicon-based embedded microchannel with three-dimensional (3D) manifold (MF) μ-cooler offers lower pressure drop and increased heat removal capability (>1 kW/cm2) for microprocessors and power electronics cooling using single-phase water. In this paper, we present a thermal–fluidic numerical analysis of silicon-embedded microchannel cooling. We develop a full-scale computational fluid dynamics (CFD) model of a large footprint (24 × 24 mm2) device having embedded microchannels and a 3D manifold. It is found that the pressure/velocity distributions at three different critical regions inside the inlet manifold have a significant impact on the temperature distribution. A previous study reported a shift of the chip temperature hot-spot at high flow rates; this study delves deep into the flow and pressure variations within the MF and cold plate (CP) that leads to this shift. This study also investigates the degree of flow maldistribution, first between the manifold channels caused by the plenum and then between the cold plate channels caused by individual MF channels. Finally, this study concludes with a comparison between two different 3D manifold inlet channel heights. The comparison reveals that the manifold with 1.5 mm thickness can reduce the pressure drop by a factor of 4 while maintaining the same thermal resistance of 0.04 K cm2/W, thus indicating an increase in the coefficient of performance (COP) by a factor of 4, compared with a manifold thickness of 0.7 mm.