The need for an accurate risk assessment procedure led to the development of various fragility and vulnerability curves, covering a wide range of building typologies. Nonlinear soil behavior and soil–structure interaction (SSI) efects play an essential role in this outcome; nevertheless, their infuence is usually neglected. While for building-specifc applications, these efects may be explicitly considered, it is currently impossible to account for such efects in large-scale seismic risk analyses. We examine the efectiveness of a broad set of fragility modifers (FM) that shift existing fragility curves appropriately to consider nonlinear soil behavior and/or SSI. We apply our method to an existing block of— mainly—residential buildings in Thessaloniki, Greece. To derive the fragility curves for the building block, we perform (i) incremental dynamic analyses of the existing individual structures considering nonlinear soil behavior and SSI, (ii) incremental dynamic analyses of the existing structures neglecting the underlying soil, (iii) fragility assessment using existing fragility curves found in literature and (iv) fragility assessment using existing fragility curves found in literature, but modifed using our proposed FM to account for nonlinear soil behavior and SSI. Next, assessment is also performed in terms of vulnerability. A comparison between the obtained results highlights the efectiveness of the proposed FM for large-scale risk assessment, and the necessity to consider soil-related efects. In particuλar, the results are compared in terms of fragility and vulnerability. Since the selection of the block is representative of the city center of Thessaloniki, our results will be indicative for city-level applications.