We present a methodology for a large-scale assessment of soil-structure interaction (SSI) effects on the vibrational characteristics and the seismic loading of structures in a real urban fabric by combining airborne monitoring techniques, field surveys and simple calculations in the realm of structural and geotechnical dynamics. The proposed procedure combines geometrical features of a building stock acquired from a LiDAR-based 3D city model, material and typology data of structures from in situ inspections in representative building blocks, geotechnical data from field surveys and strong ground motion data from seismic hazard and site effects analyses. The integrated data are employed to compute at a first stage the fundamental period of each building in the urban area by means of code-defined formulas for both fixed- and flexible-base foundation conditions, thus treating soil-structure interaction effects in a simplified manner. The seismic action in terms of spectral acceleration at the fundamental period of structures is then computed, following a series of 1D site-specific analyses of soil response under different seismic scenarios. Spatially distributed ratios of structural fundamental periods and spectral accelerations, corresponding to flexible- over fixed-base foundation conditions, are mapped in GIS environment as an index of SSI effects at large-scale. The methodology is implemented in the urban area of Kalochori located west of Thessaloniki in Greece. The examined case study showed that SSI may be significant even for low-amplitude motions and may lead to higher seismic forces compared to the fixed-base case, depending on the dynamic characteristics of the structures, the soil conditions and the shape of the response spectrum. The above may be of importance in microzonation and seismic vulnerability studies at urban-scale when a building-by-building assessment is not feasible and SSI effects are too important to be ignored.