This study explores the potential of antimicrobial agents in high-performance concrete (HPC) to combat biodeterioration without compromising compressive strength. Response surface methodology (RSM) was used to create 21 combinations of nanosized TiO2 and ZnO (ranging from 0�2 by weight of cement in HPC). Results show that ZnO negatively impacts compressive strength as its content increases from 0�2, while TiO2 enhances it by up to 17 with 2 TiO2. By optimizing TiO2 and varying ZnO within the 0�2 range, compressive strengths between 81�100 MPa can be achieved. The quadratic model, with significant statistical values, accurately depicts the effects of nanoparticles on compressive strengths. © 2023 by the authors.