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A quantitative study was conducted on 376 public medical staff in the Mekong Delta region to assess the impact of organizational structure on work motivation, engagement, and job performance. Using the least-squares method of PLS-SEM run by SmartPLS 3.0 software with non-parametric Bootstrapping 2,000 repetitions to evaluate the measurement model and structural model. The results show that formalization, integration, centralization, and organizational support significantly affect engagement and work motivation. Meanwhile, job performance was significantly affected by formalization and centralization. The study also recognized that work motivation has a strong positive impact on job performance and a significant impact on engagement in work motivation and job performance.