Engineered suspensions of nanosized particles (nanofluids) may be characterized by enhanced thermal properties. Due to the increasing need for ultrahigh performance cooling systems, nanofluids have been recently investigated as next-generation coolants for car radiators. However, the multiscale nature of nanofluids implies nontrivial relations between their design characteristics and the resulting thermo-physical properties, which are far from being fully understood. In this work, the role of fundamental heat and mass transfer mechanisms governing thermo-physical properties of nanofluids is reviewed, both from experimental and theoretical point of view. Particular focus is devoted to highlight the advantages of using nanofluids as coolants for automotive heat exchangers, and a number of design guidelines is reported for balancing thermal conductivity and viscosity enhancement in nanofluids. We hope this review may help further the translation of nanofluid technology from small-scale research laboratories to industrial application in the automotive sector.