In the structural design of serial robots, topology and dimensional parameters design are independent, making it challenging to achieve synchronous optimization design between the two. To address this issue, a topology-and-dimension-parameter integrated optimization method (TPOM) is proposed by setting critical variables to connect topology layout and dimensional features. Firstly, the topology layout is extracted by the edge detection technique. Structural manufacturability reconstruction is conducted by measuring the dimensions of the layout through a program. Additionally, for the reconstructed structural layout, critical variables are set using three-dimensional software (SOLIDWORKS2021). The experiments primarily involve critical variables, quality, and deformation as variables. Then, the response surface methodology is selected to construct the stiffness–mass metamodel, and based on this, the structural deformation is analyzed. Lastly, the multi-objective genetic algorithm (MOGA) is employed to optimize the critical variables, and an optimized structure is established for validation. The results indicate that the proposed method (TPOM) reduces the mass of the structure by 15% while maintaining its stiffness. In addition, the deformation of the whole structure is less than 0.352 mm, which meets the requirements of industrial applications. Through quantitative analysis of the experimental results, the feasibility and superiority of the proposed method have been demonstrated.