Bus rollover accidents are among the most severe traffic incidents due to the high risk of structural collapse and intrusion into the passenger survival space. Although ECE R66 provides clear safety requirements, most existing studies focus on European bus models and simplified analyses, offering limited insight into integrated reinforcement strategies tailored to regional designs. This study addresses this gap by applying finite element analysis (FEA) in Ansys LS-DYNA to evaluate and optimize structural configurations of a Vietnamese bus frame. Nine reinforcement designs were analyzed, the most efficient configuration achieved a 25.9% weight reduction while maintaining structural integrity. Further LS-OPT optimization reduced stress by 5.5% with only a 1.5% mass increase, enhancing rollover resistance. The study provides a novel, systematic approach for improving bus safety while minimizing weight.