Ever-increasing demands for precision and efficiency in ultra-precision motion systems will result in a lightweight and flexible motion system with complex dynamics. In this paper, a systematic approach is proposed where control gains, 3D structural topology and actuator configuration are integrated into optimization to derive a system-level optimal design which possesses a high vibration control performance, and still satisfies multiple design constraints. A material interpolation model with high accuracy is proposed for the integrated optimization, a simple integral equation utilizing R-functions and level-set functions is established to represent complex non-overlapping constraints of actuators. Over-actuation degrees are utilized to actively control the dominant flexible modes. Responses of residual flexible modes are restricted by increasing the coincidence of their nodal areas at actuators (sensors) locations. The objective function is the constructed worst-case vibration energy of the flexible modes. A dual-loop solving strategy combining the genetic algorithm and the modified optimal criteria method is adopted to solve the optimization problem. A fine stage in the wafer stage is designed to prove the effectiveness of the proposed method.