<p>This study aims to explore the dynamic instability of the soil-tunnel-frame structure system under seismic excitation, using a section of the Dalian Metro as the engineering background. Four different working conditions were designed, and shake table tests were performed alongside numerical simulations for comparative analysis. The Kelvin constitutive model subroutine was introduced in the numerical model, and the equivalent linear method was applied to handle the nonlinear characteristics of sandy soil during the calculation. The study focuses on the effects of peak ground motion acceleration, spectral characteristics, strain, and displacement on the dynamic response of the soil-tunnel-frame structure system. The findings reveal that the soil and tunnel structures help dissipate seismic energy, and the presence of both the tunnel and raft foundation frame decreases the system’s natural frequency. The acceleration at the top of the rectangular tunnel exceeds that at the bottom. The raft foundation frame reduces the tunnel’s acceleration response (by up to 32.8%) while amplifying its strain response (by up to 28.3%). Among different seismic wave inputs, the Kobe wave induces the highest peak acceleration and frame structure displacement, followed by the El-Centro wave, while the Chi–Chi wave causes the lowest values. The peak strain of the rectangular tunnel is mainly concentrated at the arch shoulder, and there is a positive correlation between tunnel strain and acceleration amplitude. The peak acceleration of the raft foundation frame structure increases gradually with height but shows a decreasing trend near the third-floor slab. The presence of the tunnel attenuates the acceleration and displacement responses of the raft foundation frame structure, with a maximum reduction of 39%. The above findings offer insights and guidance for further studies and seismic design of similar engineering projects involving SSSI effects.</p>