Nanofluids have gained attention for their potential to solve overheating problems in various industries. They are a mixture of a base fluid and nanoparticles dispersed on the nanoscale. The nanoparticles can be metallic, ceramic, or carbon based, depending on the desired properties. While nanofluids offer advantages, challenges such as nanoparticle agglomeration, stability, and cost effectiveness remain. Nonetheless, ongoing research aims to fully harness the potential of nanofluids in addressing overheating issues and improving thermal management in different applications. The current study is concerned with the fluid flow and heat transfer characteristics of different nanofluids using different types of nanoparticles such as Al2O3, SiO2, and ZnO mixed with different base fluids. Pure water and ethylene glycol−water (EG−H2O) mixtures at different EG−H2O ratios (ψ = 0%, 10%, 30%, 40%) are used as the base fluid. Furthermore, a rectangular microchannel heat sink is used. Mesh independent study and validation are performed to investigate the current model, and a good agreement is achieved. The numerical analysis evaluates the influence on the heat transfer coefficient and flow characteristics of nanofluids for Reynolds numbers 500 to 1200 at a 288 K inlet flow temperature. The results show that ZnO nanofluid and 40% EG−H2O increase the heat transfer coefficient by 63% compared to ZnO−H2O nanofluid obtained at Re = 1200 and φ = 5%. Conversely, the pressure drop by ZnO is nearly double that obtained by Al2O3 and SiO2.