The use of micro-channel heat exchangers is widespread across a variety of different industrial sectors. This study presents both an experimental and a numerical analysis to compare the performance of four different designs of microchannel heat sinks. The study dealt with using pure water and nanofluid (Al2O3, CuO, and TiO2–H2O) with volumetric concentrations of (0.01- 0.03) as coolants. The software Comsol Multiphysics was employed for conducting numerical analysis in order to simulate and resolve the issue pertaining to fluid and heat flow in a three-dimensional domain. A constant heat flux of 170 kW/m2 is applied to the lower wall of the four microchannels. The simulations were exclusively conducted within the laminar regime, covering a range of Reynolds numbers spanning from 50 to 150. The impact on the temperature of the microchannel's wall, thermal resistance, pressure drop, and friction factor is demonstrated. Based on the results obtained, it is evident that the utilization of nanofluid in the cooling process of a wavy and zigzag microchannel heat sink yields superior performance in terms of both heat transfer and dissipation, as compared to the implementation of pure water as the cooling medium for the heat sink.