This paper illustrates the improvement in the performance of a centrifugal pump by modifying impeller design specifications via response surface methodology (RSM) complemented with computational fluid dynamics (CFD) simulations. Impeller geometry is varied at the best efficiency point (BEP) to get hold of the performance of the pump. The pump characteristics are evaluated by studying the impeller eye diameter, vane exit angle, and width of impeller blade at exit. Different pump models were analyzed by modifying the critical design parameters via central composite design. CFD analysis is carried out for the developed models to predict the performance of the pump and experimental studies were conducted to validate the CFD. Conformation experiments were performed to verify the optimal design specifications. Good agreements between the predicted and actual values of responses have been observed. The RSM-and CFD-based optimized impeller parameters yield an increase in total head from 39.66 m to 41.72 m and the power consumption is minimized from 432.17 W to 366.95 W at BEP.