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This study focuses on experimentally investigating the thermal-hydraulic performance of an automotive radiator operating with nanofluids at high temperatures, from 80 °C to 105 °C, from a binary mixture of water and ethylene glycol (50% by volume), served as the base fluid. Nanofluids were prepared by dispersing multi-walled carbon nanotubes (with volumetric concentrations of 0.025%, 0.05%, and 0.1%) and silver (with volumetric concentrations of 0.001%, 0.002%, and 0.003%) nanoparticles using a two-step method involving ultrasonication and high-pressure homogenization. As a first step, the stability of the nanofluid samples was assessed using the UV-vis spectrophotometry method, followed by an experimental measurement of their thermophysical properties, including thermal conductivity, viscosity, and specific mass. Subsequently, the nanofluids were employed as a substitute for coolant fluids in a car radiator installed in a wind tunnel instrumented to evaluate thermo-hydraulic performance. Key factors affecting heat transfer and pressure drop, such as nanoparticle concentration, mass flow rate, and temperature, were thoroughly investigated. The computational approach was developed in the Engineering Equation Solver (EES) software to simulate the radiator. The results show that the thermal conductivity of the nanofluids increased by up to 6.4%. The maximum increases observed in viscosity and specific mass were 11% and 0.23%, respectively. The models proposed for estimating thermal conductivity (maximum deviation 1.5%) and viscosity (maximum deviation 3%) were found to be suitable, exhibiting good agreement with experimental results. For the tests on the experimental bench, the nanofluids demonstrated a slightly enhanced heat transfer rate, with a maximum value of 3.7% compared to the base fluid. However, this improvement was accompanied by an increase in pumping power of 3.6%, moderately impacting the thermal-hydraulic performance coefficient. Furthermore, laminar heat transfer outcomes were compared with the values obtained from the correlation models for nanofluids, obtaining an average deviation of 4.1%. In general, silver nanofluids did not show the potential to substitute coolant for car radiators. On the other hand, the MWCNT2 nanofluid sample with carbon nanotube proved to be promising, exhibiting a thermal-hydraulic coefficient of performance of 1.015.