In this work, a CFD modeling of a horizontal circular tube was presented to investigate the effect of nanofluids on laminar forced convective heat transfer. The water-based Al2O3 and Al2O3–Cu hybrid nanofluid with 0.1% volume concentration and average particle size of 15 nm was considered. The solutions were based on both single- and two-phase approaches. The results showed a higher convective heat transfer coefficient for the hybrid nanofluid. In comparison to the single phase approach, the proposed mixture model revealed a better agreement with the experimental data. An energetic performance of fluid flowing was evaluated too. For these hybrid nanofluids, the average Nusselt number increase was 4.73% and 13.46% in compared to Al2O3/water and pure water, respectively.