Nanofluid, the fluid suspensions of a metallic nanoparticle, became a coolant fluid that is used when a promising enhancement in heat transfer is required. In the current study, the characteristics of fluid flow and heat transfer are numerically investigated using different nanofluids (Al2O3−H2O, TiO2−H2O, and SiO2−H2O) and different micro-channel heat sink (MCHS) configurations (rectangular, triangular, trapezoidal, and circular). In this numerical investigation, the effect of Re number ranged from 890 to 1500, and the effect of nanoparticle concentration ranged from 1% to 7% at constant heat flux q = 106 W/m2, and constant fluid inlet temperature of 288 K, were studied. The average heat transfer coefficient, h, and pressure drop, Δp, are used to quantify the fluid flow and heat transfer characteristics in each MCHS configuration and for each nanoparticle concentration. It is revealed that a better heat transfer coefficient is obtained for Al2O−H2O compared with other types of nanoparticles and pure water, such as 8.58% heat transfer coefficient improvement obtained at Re = 1500 and φ=7% more than that of pure water. It is also inferred that the maximum heat transfer coefficient is obtained by the triangular MCHS; however, it has the highest pressure drop because of the lowest hydraulic diameter.