The large number of catastrophic earthquakes that have occurred worldwide and their consequences point out the fact that the seismo-geological structure of the terrain represents an amplitude-frequency modifier of the seismic effect. The unconsolidated sediments lying upon the bedrock as well as the variations of the bedrock topography may increase the amplification potential of the seismic effects depending on their physical properties and thickness. From this aspect, there arises the need for obtaining as realistic as possible insight into the structure of the terrain, i.e., definition of the geometry of the sedimentary basins. Particular attention in this study was paid to definition of thickness variation of alluvial unconsolidated deposits that constitute the Skopje sedimentary basin, reaching a depth of down to 200 m, as well as the topography of the Neogene sediments present in the terrain base. For that purpose, preliminary 3D geological modelling was done by interpolation of a number of boreholes made in the urban area of Skopje city. Geophysical surveys were performed by application of active and passive seismic methods as are seismic refraction, seismic reflection, Multichannel Analysis of Surface Waves (MASW), Refraction Microtremor (REMI) and Horizontal-to-Vertical Spectral Ratio (HVSR) for the purpose of defining the variation of the shear-wave velocity Vs through different lithological layers as well as upgrading and improving the accuracy of the 3D model. Of particular importance for this survey was the implementation of fast, economical and efficient procedure by using the combined seismic methods approach, which enabled seismo-geological modeling to different scales as well as comparative analysis of the results and verification of their accuracy.