This paper presents results from numerical simulations validated by experimental results related to the effects of DSSI on the dynamic response of bridges. An in-service overpass was shaken using the T-Rex, a large-amplitude mobile shaker from the National Hazards Engineering Research Infrastructure (NHERI) facilities. Studies implementing Finite Element Modeling to develop time histories, response spectra, and eigenmodes were conducted in a forward-modeling problem setup. Two models were created to assess the DSSI effects on the dynamic response of the bridge. One model included elements that incorporate DSSI effects, while the other had fixed-base boundary conditions. The response from the DSSI FEM model matched the field results better than the fixed-base model, in terms of the peak response amplitudes and identified natural frequencies and modes. The influence of a series of factors, such as the soil shear wave velocity, bridge height, bridge foundation embedment depth and the corresponding rigidity, slenderness, and embedment ratios, on the bridge response is presented.