Conventional buildings made of reinforced concrete (r/c) or steel are practically encountered daily in common construction practice. Current regulations offer complete guidance on the seismic design and dimensioning of typical structures made of the same structural material throughout. Nevertheless, in the case of a structure constructed with r/c structural elements at the lower part and steel structural elements at the upper part, forming a so-called hybrid steel-r/c building is common. The present regulations do not address hybrid buildings in design or dimensioning. This study aims to fill this gap in the literature by comparing the seismic performance of 3D hybrid buildings to conventional r/c and steel buildings. Three sets of buildings are designed and dimensioned, namely r/c buildings, steel ones, and hybrid steel-r/c ones. The considered r/c, steel, and hybrid models are subjected to the same strong ground excitations using a nonlinear time history analysis, considering the potential impact of the excitation orientation. Especially for hybrid models, two limit interconnection conditions are dealt with, characterized here as a "fixed" or "fixed-pinned" support of the steel part upon the r/c one. Unitless parameters are selected to compare the seismic response diagrams to determine the most detrimental structural effect. The advantages and disadvantages of r/c, steel, and hybrid buildings are comparatively discussed in terms of seismic resilience, noting that a hybrid configuration provides a promising alternative for seismic performance compared to typical constructions, thus providing enhanced possibilities in structural design. The analysis results show that fewer structural failures occur for hybrid buildings compared to conventional ones when subjected to the same earthquake excitations. The findings suggest that hybrid buildings could be a viable solution for practical construction projects, particularly in seismic-prone areas.