Under human-induced excitations, a floor structure may suffer excessive vibrations due to its large span and low damping ratio. Vertical vibrations, in particular, can become intolerable during resonance events. A tuned mass damper (TMD) is a widely used single-degree-of-freedom dynamic vibration absorber. To enhance the serviceability of a floor structure, a multiple TMD (MTMD) system finds broad application. The parameters of the MTMD must be carefully designed to achieve satisfactory performance. However, existing studies often employ a simplified model of the floor structure with closely spaced modes to optimize the parameters of MTMD. Nonetheless, an oversimplified floor model can lead to a reduction in its control effect. To solve this problem, this study utilizes the OAPI facility of SAP2000 to build a connection with MATLAB. A multi-objective optimization algorithm based on the artificial fish swarm algorithm (AFSA) for MTMD is developed in MATLAB, while the finite element model of a real floor structure is built in SAP2000. The locations of the MTMD system are initially specified in SAP2000 and, through the proposed MATLAB–SAP2000 interface, data can be exchanged between them. Based on the structural dynamic responses to external excitations in SAP2000, the optimization process for the MTMD is carried out in MATLAB. Concurrently, the parameters of the MTMD in SAP2000 are iteratively adjusted until they reach their final optimal values. To underscore the enhancements brought about by the proposed interface and optimization method, a comparative case study is conducted. A group of MTMDs, optimized using a conventional method, is presented for reference. The numerical results indicate that, overall, the proposed MTMD system exhibits superior control effectiveness and robustness.