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This systematic review investigates optimization models applied to healthcare and pharmaceutical supply chains between 2015 and 2025, emphasizing mathematical formulations, computational methods, and validation practices. Following PRISMA-based procedures, 118 records were identified, resulting in a final sample of 37 studies. Results reveal the predominance of mixed-integer linear programming, especially in network design, facility location, inventory control, and integrated production-distribution planning. The literature also shows increasing adoption of multi-objective optimization, stochastic programming, robust optimization, heuristics, metaheuristics, and hybrid simulation-optimization approaches. Although methodological sophistication has advanced, validation practices remain concentrated in synthetic experiments, with limited real-world application. Relevant gaps include low reproducibility, scarcity of benchmark instances, and insufficient reporting of computational metrics. The review proposes a structured taxonomy of methods and a future research agenda involving scalable exact methods and integration with artificial intelligence.
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