This research presents novel findings by exploring the synergistic effects of incorporating nano-sized titanium dioxide (TiO₂) and zinc oxide (ZnO) nanoparticles into a high-performance concrete (HPC) matrix. The study utilized Response Surface Methodology (RSM) to determine the optimal combinations of TiO₂ and ZnO for achieving peak performance within the matrix. Various combinations of TiO₂ and ZnO, ranging from 0 % to 2 %, were incorporated into HPC mixes, focusing on evaluating their effects on compressive strength (CS), splitting tensile strength (STS), flexural strength (FS), durability, and photocatalytic properties. The results revealed that maintaining higher proportions of TiO₂ over ZnO led to superior mechanical properties, with the most effective combination determined to be 2 % TiO₂ and 1.33 % ZnO, which agrees with the prediction by the RSM model and verified through experimental testing. However, these combinations did not significantly enhance the durability properties of the HPC samples when exposed to acidic curing for three months.On the other hand, the photocatalytic properties of HPCs with different combinations of TiO₂ and ZnO were significantly improved. The combination with the maximum content of both nanoparticles had only 23.7 % of Rhodamine B remaining on its surface after 100 hours of UV radiation. Comparing the individual effects of TiO₂ with ZnO, it was observed that a higher TiO₂ dosage (2 %) caused earlier Rhodamine B discolouration compared to a higher ZnO dosage (2 %). Therefore, based on the photocatalytic degradation efficiency, it was concluded that the concrete can confer self-cleaning properties under UV radiation and serve as a precursor for developing self-cleaning concrete composites for more sustainable and resilient structures.