Since centrifugal pumps consume a mammoth amount of energy in various industrial applications, their design and optimization are highly relevant to saving maximum energy and increasing the system’s efficiency. In the current investigation, a centrifugal pump has been designed and optimized. The study has been carried out for the specific application of transportation of slurry at a flow rate of m3/hr to a head of 20 m. For the optimization process, a multi-objective genetic algorithm (MOGA) and response surface methodology (RSM) have been employed. The process is based on the mean line design of the pump. It utilizes six geometric parameters as design variables, i.e., number of vanes, inlet beta shroud, exit beta shroud, hub inlet blade draft, Rake angle, and the impeller’s rotational speed. The objective functions employed are pump power, hydraulic efficiency, volumetric efficiency, and pump efficiency. In this reference, five different software packages, i.e., ANSYS Vista, ANSYS DesignModeler, response surface optimization software, and ANSYS CFX, were coupled to achieve the optimized design of the pump geometry. Characteristic maps were generated using simulations conducted for 45 points. Additionally, erosion rate was predicted using 3-D numerical simulations under various conditions. Finally, the transient behavior of the pump, being the highlight of the study, was evaluated. Results suggest that the maximum fluctuation in the local pressure and stresses on the cases correspond to a phase angle of 0°–30° of the casing that in turn corresponds to the maximum erosion rates in the region.