Lateral inflow forebay is inevitably utilized to connect the diversion and inlet passage in water transport engineering, because of geographical and construction constraints. However, the flow in the lateral inlet forebay is very easy to generate undesirable flow patterns (such as the flow separation and backflow) leading to vibration and low operating efficiency. In this study, the geometric parameters were optimized for the lateral inlet forebay of the pump sump using Computational Fluid Dynamics (CFD) and Response Surface Method (RSM), in order to improve the flow pattern for the high efficiency of the pump unit. Firstly, the parametric design was realized for the lateral inflow forebay of the pump sump using the 3D modeling software NX 10.0. There were the specified parameters associated with the Workbench, such as the diffusion angle α, slope β, and turning angle γ of the lateral inlet forebay. Secondly, the typical Box-Behnke Design (BBD) was selected to determine the three factors and three levels test. 17 groups of test schemes were obtained to simulate the flow field of the lateral inlet structure under the Fluent platform. Thirdly, the optimization target was selected as the uniformity of velocity distribution at the horn tube outlet section. The second-order polynomial regression equation was utilized to establish the regression equation of velocity distribution uniformity at the horn tube outlet section and geometric parameters, namely the diffusion angle α, slope β, and turning angle γ of the lateral inlet forebay. Subsequently, the significance of the regression equation was evaluated by the analysis of variance. As such, the regression equation reflected the relationship between the response values and factors. The maximum uniformity of velocity distribution at the outlet section was selected as the response target to determine the optimal parameter combination. Finally, the internal flow characteristics of the optimal lateral inlet structure were compared with the original model, including the uniformity of velocity distribution and the velocity-weighted average drift angle. Results indicate that there was a significant influence of the diffusion angle α, slope β, and turning angle γ on the velocity distribution uniformity at the horn tube outlet section. Among them, the most significant was the turning angle γ, whereas, the less significant was the slope β. Furthermore, there was no significance of the slope β, and the turning angle γ on the coupling effect of velocity distribution uniformity at the outlet section. By contrast, the diffusion angle and turning angle posed the most significance on the coupled uniformity of velocity distribution at the outlet section, in terms of the interaction between the diffusion angle α, and slope β. Moreover, there was the greatest influence of the interaction between the diffusion angle α and the turning angle γ. But, the least influence was found in the interaction between the diffusion angle α and the slope β. An optimal uniformity of the velocity distribution was achieved at the horn tube outlet section under the lateral inlet forebay with the diffusion angle α of 10°-13°, the slope β of 8°-9°, and the turning angle γ of 74°-75°. Compared with the original model, the cross-sectional velocity distribution uniformity of the optimized lateral inlet structure under design water level increased by 23.41 percentage points at least, and the velocity-weighted average drift angle increased by 13.95°, similarly, under low water level, the cross-sectional velocity distribution uniformity of the optimized lateral inlet structure increased by 18.30 percentage points at least, and the velocity-weighted average drift angle increased by 14.79°. More importantly, there was no deflected flow and large-area reflux in the channel. These findings can provide the positive significance to promote an optimal design of the lateral inlet structure of the pump sump.