This study investigates the influence of phases interactions in hybrid nanofluids using a multiphase mixture model. Neglecting phase interaction for Al2O3-Cu leads to Nusselt number difference of 0.05 (volume fraction 0.1%), increasing to 0.6 at volume fraction 2%. Among investigated nanofluids (Al2O3-Au NPs, Al2O3-CuO, Al2O3-TiO2, CuO-Au NPs, CuO-TiO2, TiO2-Au NPs), those with gold nanoparticles exhibit exceptional heat transfer enhancements: Al2O3-Au NPs (63.85%), CuO-Au NPs (64.65%), and TiO2-Au NPs (62.10%) at 3% total solid phase volume fraction. CuO-Au NPs perform best, except at ∼5% volume fraction where Al2O3-Au NPs excel. Optimization shows increasing gold particle volume fractions benefit particularly at higher Reynolds numbers. For CuO-Au NPs, highest average Nusselt numbers are obtained at gold volume fractions of 10%, 20%, 40%, and 60% of total solid phases volume fractions for Reynolds numbers 300, 500, 1000, and 2000, respectively. Moreover, the investigation showed that the performance index generally increases with volume fraction up to 5%, except for hybrid nanofluids with gold particles. Notably, in the presence of gold particles, the performance index rises distinctly up to a volume fraction of 3%, followed by a subsequent decline.