The increasing demand for sustainable building materials has motivated the search for alternative supplementary cementitious materials to reduce the use of Portland cement while maintaining concrete performance. The present study aims to investigate the synergistic effects of bagasse ash (BA) and rice husk ash (RHA) as partial cement replacements in ternary blended concrete. Previous studies used agricultural ashes individually or in binary form only, whereas in the present work, the synergistic effect of BA and RHA is systematically studied, and Response Surface Methodology (RSM) is used to develop predictive models and optimize the performance of concrete. The slump, compressive strength and splitting tensile strength were evaluated using a Central Composite Design (CCD) to determine the effect of the levels of replacement of BA and RHA. Quadratic regression models were built and evaluated using analysis of variance (ANOVA). All models were statistically significant (p < 0.05) and had high predictive accuracy (R² > 0.92). The results revealed that increases in BA and RHA contents reduced the workability because of their high specific surface areas and porous structures, while moderate combinations improved the compressive and splitting tensile strengths due to the synergistic filler effects, secondary pozzolanic reactions, and matrix densification. The multi-objective optimization based on the desirability function provided an optimal mixture of 5% BA and 15% RHA with an overall desirability of 92.8%, which provided the best compromise between workability and mechanical performance. Experimental validation of the optimized mixture showed good agreement of the model predictions with prediction errors of less than 5%, confirming the reliability and robustness of the developed RSM models. The results show that synergistic use of BA and RHA is a feasible and sustainable solution for producing high-performance ternary blended concrete and provides a reliable framework for the optimization of the mixture.