Improvements in heat exchanger thermal efficiency are crucial for achieving energy use and cost reductions. The use of nanofluids and the rotation of the exchanger inner tube may enhance heat transfer and exchanger efficiency. In this work, after having performed experiments on such a heat exchanger, a three dimensional numerical model was developed to simulate the transitional forced convection flow of a horizontal double-tube heat exchanger, with the aim of obtaining insight into the effects of the inner tube rotation, fluid flow rate and type of nanofluid employed. It was found that an increase in the nanoparticle concentration up to 3% increased the exchanger efficiency. Al2O3, Al2O3-Cu and Cu-water nanofluids were studied, with the Cu-water being the fluid with the best performance (19.33% improvement). Heat transfer was enhanced with inner tube rotation up to 500 rpm (41.2%). Nevertheless, pressure drop and friction values were increased due to both phenomena, leading to higher pumping power values for the operation of the heat exchanger. Hence, a balance between the performance and pumping power increase must be considered when modifications are made on a heat exchanger. The development of the numerical model might help in further optimizing, redesigning and scaling up heat exchangers.