AbstractStory isolation systems (SIS) have great application potential in the seismic design of some special structures. This paper studied the seismic control performance of SIS using a tuned mass damper inerter (TMDI) considering two installation modes, namely TMDI-A and TMDI-B. First, a four-degree-of-freedom (4DOF) simplified model including the masses of the substructure, superstructure, isolation layer, and TMDI is proposed, and three cases with different isolation layer locations were designed. Second, numerical optimization based on the H2 norm was used to obtain the optimal parameters of the TMDI considering the influence of the tuned mass ratio and the design period and damping of the isolation layer. Third, a comparative study was conducted on the optimal performance of the TMDI-A and TMDI-B schemes compared with their corresponding tuned mass damper (TMD) schemes (i.e., TMD-A and TMD-B) by time-history analysis. Finally, an 11-story SIS was designed as an example to investigate the effectiveness of the TMDI in a multistory structure. Results showed that the optimal performance of the two TMDI schemes can be significantly enhanced with the increase of the inertance–mass ratio, and also will be improved with the rise of the isolation layer location, whereas the increase of the tuned mass ratio had a converse effect on the performance of TMDI-A and TMDI-B. In addition, both TMDI schemes had better performance when the isolation layer was in a low-damping state, and the isolated period of the superstructure only affected the control performance of the TMDI-B scheme. In summary, the TMDI schemes had remarkable superiority over the TMD schemes, and TMDI-B had better performance than the TMDI-A scheme, which was verified by the analysis of the simplified model and the multistory structure.