Following effective seismic codes, common buildings are considered to be made of the same material throughout the story distribution and based on an ideal rigid soil. However, in daily construction practice, there are often cases of buildings formed by a bottom part constructed with reinforced concrete (r/c) and a higher steel part, despite this construction type not being recognized by code assumptions. In addition, soil deformability, commonly referred to as the Soil–Structure Interaction (SSI), is widely found to affect the earthquake response of typical residence structures, apart from special structures, though it is not included in the normative design procedure. This work studies the seismic response of in-height mixed 3D models, considering the effect of sustaining deformable ground compared to the common rigid soil hypothesis, which has not been clarified so far in the literature. Two types of soft soil, as well as the rigid soil assumption, acting as a reference point, are considered, while two limit interconnections between the steel part on the concrete part are included in the group analysis. The possible influence of the seismic orientation angle is explored in the analysis set. Selected numerical results of the dynamic nonlinear analyses under strong near-fault ground excitations were plotted through dimensionless parameters to facilitate an objective comparative discussion. The effect of SSI on the nonlinear performance of three-dimensional mixed models is identified, which serves as the primary contribution of this work, making it unique among the numerous research works available globally and pointing to findings that are useful for the enhancement of the seismic rules regarding the design and analysis of code-neglected mixed buildings.