To realize Mo-99 production method using an accelerator, an optimal cooling design of gamma-ray converter is necessary. Generally, designers sample the design variables and calculate the temperature distribution by multiphysics analysis repeatedly to obtain an optimal design. However, this process takes high calculation cost to achieve the optimal result because of the increase in the number of finite elements and poor convergence. We have proposed more efficient design technique that divide the analysis model into upstream and midstream sections. First, the inlet boundary condition of the midstream section was optimized by response surface method, to find an optimal flow velocity distribution which minimize the maximum temperature of the converter. Second, the upstream section was designed to obtain the optimal flow velocity distribution. The results demonstrate that venturi structure can control the flow and efficiently cool the case section of the converter, which is the possible bottleneck.