Although post-tensioning constitutes an advanced technology in civil engineering, its seismic design guidelines are not yet well established, particularly for cast-in-place reinforced concrete buildings. From this perspective, this study experimentally investigates the seismic performance of post-tensioned cast-in-place reinforced concrete sub-assemblages, complemented by numerical simulations of reinforced concrete frame systems incorporating post-tensioned beams. In the laboratory program, the mild steel ratio, load-balancing ratio, and joint geometry were selected as the primary variables. Following satisfactory calibration between the experimental observations and the numerical models, nonlinear time-history analyses were conducted on prototype buildings to determine seismic response modification factors. Based on the available data employed in this study, both graphical and closed-form solutions were proposed for the response modification factors as a function of interstory drift ratio. The results indicate that a response modification factor lower than that prescribed for ductile moment-resisting frames is more appropriate for post-tensioned cast-in-place reinforced concrete structural systems.