The problem of the through-soil coupling of structures has puzzled the researchers in the field for a long while, especially regarding the varied performance of identical, adjacent buildings in earthquakes. The phenomenon of structure-soil-structure interaction (SSSI) that has often been overlooked is recently being recognized: The possible effects in urban regions are yet to be thoroughly quantified. In this respect, the goal of this work was to rigorously investigate the interacting effects of adjacent buildings in a two-dimensional setting. Detailed finite element models of 5-, 15-, and 30-story structures, realistically designed, were used in forming building clusters on the viscoelastic half-space. Perfectly matched layers were used to properly define the half-space boundaries. The interaction of the structure and the soil medium because of the presence of spatially varying ground motion on the boundary of excavated region was considered. The effects of the foundation material and the distance between adjacent buildings on the structural behavior of the neighboring buildings were investigated using drift ratios and base shear quantities as the engineering demand parameters of interest. The effects of SSSI, first investigated in the frequency domain, was then quantified in the time domain using suites of appropriate ground motions in accordance with the soil conditions, and the results were compared with the counterpart SSI solution of a single building. The results showed that, for identical low-rise structures, the effects of SSSI were negligible. Yet, neglecting SSSI for neighboring closely spaced high-rise structures or building clusters with a large stiffness contrast was shown to lead to a considerable underestimation of the true seismic demands even compared with solutions obtained using the rigid base assumption.