This study addresses the critical need to understand the seismic behavior of cable-stayed bridges under Multi-Support Excitation (MSE) in order to mitigate earthquake-induced damage to these structures. The primary focus is on the investigation of response amplification phenomena and their seismic implications for cable-stayed bridges. Through a detailed comparative analysis of MSE and Synchronous Excitation (SE) across various structural locations, the study evaluates the impact of site-specific recorded ground motions of different earthquake categories. A pragmatic framework is developed to simulate realistic MSE ground motions for diverse earthquake scenarios, emphasizing the necessity of considering MSE in bridge design. The findings reveal a significant amplification of the design requirements due to antisymmetric mode excitation and increased tower and pier motions. The study also identified the need for in-depth analysis of cable-stayed bridges to address the increased vulnerability of tower-adjacent areas and to devise targeted reinforcement strategies of vulnerable components. These insights are critical for advancing seismic design practices and improving the resilience of cable-stayed bridges, contributing to safer urban infrastructure.