In the territory of Dushanbe city, the capital of Tajikistan, detailed geological and geophysical data were collected during geophysical surveys in 2019–2020. The data comprise 5 microtremor array measurements, 9 seismic refraction tomography profiles, seismological data from 5 temporary seismic stations for standard spectral ratio calculations, 60 borehole datasets, and 175 ambient noise measurements. The complete dataset for Dushanbe was used to build a consistent 3D geologic model of the city with a size of 12 × 12 km2. The results of the seismological and geophysical surveys were compared and calibrated with borehole data to define the boundaries of each layer in the study area. The Leapfrog Works software was utilized to create a 3D geomodel. From the 3D geomodel, we extracted six 12 km long 2D geological cross-sections. These 2D geological cross-sections were used for 2D dynamic numerical modeling with the Universal Distinct Element Code software to calculate the local seismic response. Finally, the dynamic numerical modeling results were compared with the amplification functions obtained from the seismological and ambient noise data analysis. The 2D dynamic numerical modeling results allowed a better assessment of the site effects in the study area to support seismic microzonation and the determination of local peak ground acceleration changes in combination with regional seismic hazard maps. In addition, our results confirm the strong seismic amplification effects noted in some previous studies, which are attributed to the influence of local topographic and subsurface characteristics on seismic ground motions.