Marine sediment pumps are extensively applied in marine engineering fields with complex media and harsh flow conditions. Therefore, this study conducts a multi-factor optimization design for a marine sediment pump. The response surface optimization method is utilized to improve the efficiency by optimizing the number of impeller blades, the blade inlet angle, the blade outlet angle, and the blade wrap angle. Next, a response surface regression model is created, and the influence of geometric parameters on the efficiency is determined. Meanwhile, the energy loss mechanism and vortical structure characteristics after optimization are analyzed by applying entropy production and the method for identifying Omega vortices. The findings suggest a 6.33% efficiency enhancement in the optimized model under the design conditions. The impeller’s internal flow field is enhanced, and the entropy generation rate is significantly diminished. The fluid flow adhered more closely to the blade profile, and the velocity and pressure distribution exhibit better uniformity. The presence of large-scale vortices and occurrences of flow separation within the impeller passage experience a notable decrease, and the overall fluid pressure fluctuation amplitude decreased, resulting in a more stable flow. Therefore, the discoveries from the research offer references for the design and selection of marine sediment pumps.