Vibration-assisted machining, a hybrid processing method, has been gaining considerable interest recently due to its advantages, such as increasing material removal rate, enhancing surface quality, reducing cutting forces and tool wear, improving tool life, or minimizing burr formation. Special equipment must be designed to integrate the additional vibration energy into the traditional system to exploit those spectacular characteristics. This paper proposes the design of a new 2-DOF high-precision compliant positioning mechanism using an optimization process combining the response surface method, finite element method, and Six Sigma analysis into a multi-objective genetic algorithm. The TOPSIS method is also used to select the best solution from the Pareto solution set. The optimum design was fabricated to assess its performance in a vibration-assisted milling experiment concerning surface roughness criteria. The results demonstrate significant enhancement in both the manufacturing criteria of surface quality and the design approach criteria since it eliminates modeling errors associated with analytical approaches during the synthesis and analysis of compliant mechanisms.