The pumping power diminution consequent to the use of nanoparticle suspensions as heat transfer fluids is analyzed theoretically assuming that nanofluids behave like single-phase fluids. In this hypothesis, all the heat transfer and friction factor correlations originally developed for single-phase flows can be used also for nanoparticle suspensions, provided that the thermophysical properties appearing in them are the nanofluid effective properties calculated at the reference temperature. In this regard, two empirical equations, based on a wide variety of experimental data reported in the literature, are used for the evaluation of the nanofluid effective thermal conductivity and dynamic viscosity. Conversely, the other effective properties are computed by the traditional mixing theory. Both laminar and turbulent flow regimes are investigated, using the operating conditions, the nanoparticle diameter, and the solid–liquid combination as control parameters. The fundamental result obtained is the existence of an optimal particle loading for minimum cost of operation at constant heat transfer rate. A set of empirical dimensional algebraic equations is proposed to determine the optimal particle loading of water-based nanofluids.