The improvement of performance and applications that include the convection heat transfer process is extremely related to the thermophysical properties of the fluids. However, it was found that adding nanoparticles to the conventional fluids (known as nanofluids) is an advanced way to enhance their thermophysical properties leading to an enhanced heat transfer process. This study presents a numerical approach to investigate the laminar flow-based convective heat transfer of Al2O3 nanofluids in a mini-tube under constant heat flux boundary conditions (15 kW/m2) and at an inlet temperature of 25°C. For this study, the nanofluid samples are prepared for several concentrations of Al2O3 nanoparticles and ethylene glycol/water mixture as a base fluid. Also, the thermal properties of nanofluids and base fluid are characterized. Computational fluid dynamics tools are used to develop a numerical model and validate it in comparison to experimental data. The results are discussed based on the heat transfer coefficient, considering the entrance area, pressure drop, and friction factor to determine the performance of nanofluids in comparison to the base fluid. A considerable enhancement in the heat transfer, especially in the entrance area up to 17.8%, with a corresponding increase in the pressures drop, friction factor, and the required pumping power of the nanofluids was observed.