Pushover analysis has been recommended as a reliable tool to estimate the seismic capacity of the structures. Vertical irregular structures are highly vulnerable during earthquakes due to stiffness irregularity in their elevations. Hence, seismic capacities of these types of structures need to be re-estimated during structural design stage. So, in this paper, an attempt has been made to assess the actual seismic performance of buildings with two common types of vertical irregularities such as; soft story and setback in comparison with regular (reference) building. These types of vertical irregularities are studied in individual cases, combined in one story, and combined in two different stories of the building models, while most previous studies satisfy with individual type of vertical irregularity case in the studied model. In addition, combined vertical irregularity generates extra weak points, which alter the seismic capacities, failure mode mechanism, and performance point location. Three-dimensional numerical models are created to find out significant response demand such as; the variation in periods of vibration, lateral displacement, inter-story drift, pushover curve, and plastic hinges formation. The results showed that vertical irregular buildings are subjected to early damages and have less seismic capacity than regular one. The fundamental time period becomes misleading term in seismic force calculation for vertical geometric irregular buildings and needs to be re-considered. In addition, extra lateral displacement and inter-story drift are passively generated in the vertical irregular buildings due to sudden change in stiffness. Significant negative variation in the pushover curves, ductility ratios, and plastic hinges' formation is observed when combinations of pre-mentioned vertical irregularity cases occur. Buildings with open soft ground story with asymmetric setback should have additional precautions from international codes during structural design stage according to their irregularity ratio. Therefore, response modification/reduction factor (R) may be scaled-down to adapt these negative variation in seismic capacities.