<p>The seismic vulnerability of reinforced concrete buildings with soft-storey configurations poses a significant risk in earthquake-prone regions, such as Southern Europe. The lack of infill walls on the ground floor creates a pronounced stiffness irregularity along the building’s height, resulting in a soft-storey mechanism during seismic events. This study primarily aimed to characterize the seismic behaviour of a four-story building by analyzing three scenarios of infill wall distribution (no infill walls, infill walls on all floors, and the absence of infill walls solely on the ground floor). Three types of masonry infill walls were evaluated (clay and concrete masonry units). Modal and nonlinear static adaptive pushover analyses highlighted the importance of infill walls for seismic performance, with observed stiffness increases of up to 13.55 times and strength increases of up to 2.07 times. The study’s secondary objective was to assess several retrofitting solutions’ effectiveness and identify the most cost-effective options. The retrofitting solutions examined included the addition of reinforced concrete shear walls, reinforced concrete column jacketing, and supplementary infill walls.</p>