The seismic SSSI effects in the nuclear island buildings for a representative plant are considered. The nuclear island consists of four buildings. The seismic SSSI effects on the lightest and smallest building (building of interest) are analyzed with two different approaches (ASCE 4-16, 2017). First, a model that includes all four buildings (explicit SSSI model) is constructed and used for the SSI analysis under a reference ground motion. This represents a rigorous approach that streamlines the steps necessary, but increases the complexity and size of the analysis model. However, taking advantage of high performance computing capabilities (HPC), the time and effort of the analysis remain within reasonable limits. Second, a two-step procedure is used for an approximate study of the SSSI effects on the building of interest: (1) a model that excludes the building of interest, but includes all other three buildings within the nuclear island (neighbor buildings model) is used for a seismic analysis with a reference ground motion to calculate the seismic response as acceleration time histories at various points on the soil at the footprint of the building of interest, which are used to create a modified input motion that includes the effects of the nearby buildings; and (2) the modified input motion is used for a seismic analysis of a stand-alone SSI model of the building of interest. This represents a simplified approach, which is computationally less intensive, but restricts the interaction only to the input motion and neglects to consider the mutual interaction between buildings during their seismic response. The SSSI effects are evaluated comparing the seismic response of the lightest and smallest building (building of interest) from the explicit SSSI model with the response of the same building of interest without SSSI effects, using a model with no other buildings included (stand-alone SSI model) both under a reference ground motion. The structural response from the rigorous approach is compared with the response from the simplified approach to assess the effectiveness and limitations of the simplified approach. It is found that the response spectra results from the simplified approach significantly overestimates the peak response amplitude compared to the response spectra results from the rigorous approach.