In a pioneering way, this thorough research develops and tests a new mathematical programming framework for Human Factors and Ergonomics (HFE) optimization in hospitals. The main focus is a mixed-integer linear programming model that takes into account, at the same time, operating room scheduling on the basis of patient safety, staff well-being, operational efficiency, and resource allocation. By conducting very large computational trials through the MATLAB optimization toolbox, we show the model's ability to produce schedules that not only put critical clinical tasks first but also keep the staff workloads balanced. Our findings demonstrate different fundamental aspects: optimal solutions in a way prioritize high-risk procedures, disclose the natural capacities of the system, and point out where the workflow can be improved. The optimization has been able to assign all the critical tasks (appendectomy, intubation, and code blue) without workload imbalances among the clinical staff. Nonetheless, it also revealed that the resources indeed were not fully utilized and thus more patients could be treated. This study is a very reliable tool for the healthcare managers to make evidence-based scheduling decisions that are in the time period of the hospitals and are reconcilable with the other objectives in the complex clinical environment as well.