In earlier earthquakes, irregular reinforced concrete building designs caused several failures. The irregular setback caused by the rapid drop in lateral dimension at specific altitudes might be harmful for constructions of varied heights. Engineers employ simplified nonlinear static analytical methods like pushover analysis to assess reinforced concrete structures due to their ease of use. Conventional pushover analysis covers low-rise buildings well. These approaches fail for medium- and high-rise buildings because their seismic performance depends on elements other than their basic mode shape. In response to this issue, several researchers have suggested advanced methods that consider the impact of higher-mode shapes. Nonetheless, there is a lack of scholarly research on the use of these techniques in the context of three-dimensional high-rise structures that exhibit irregular setbacks. This research performed a nonlinear pushover analysis on six models of medium- and high-rise buildings that had setback irregularities at various locations. In accordance with ASCE 7-22, the research used conventional pushover techniques, such as TLP, FLP, and ULP, and upper bound methods (MUB, EUB). The aim was to assess the suitability of these methods by comparing their results with the reference solutions of the Nonlinear Time History Analysis Method (NLTHA). The evaluation of the results was conducted by considering seismic demand criteria, such as lateral displacements, interstory drift ratios, and plastic hinge rotations. The EUB method was more accurate at finding interstory drift ratios for different types of irregular building models than the TLP, FLP, and ULP methods that are usually used for pushover analysis. The proposed method usually yields better and similar outcomes to NLTHA. Conventional approaches for predicting plastic hinge rotations at the top levels of 6- and 12-story building models failed. However, EUB and MUB accurately estimated plastic hinge rotations for irregular models.