<p>Aflatoxin B1 (AFB1), one of the most hazardous environmental and foodborne mycotoxins, is a major contributor to the global burden of hepatocellular carcinoma owing to its potent hepatocarcinogenicity and persistence throughout food systems. Although risk assessment and monitoring programs for aflatoxins have been established worldwide, the dynamic patterns of AFB1-related disease burden from production to consumption have been largely overlooked, limiting the development of truly risk-based monitoring strategies. Here, we present an integrated framework that quantifies seasonal and regional occurrence of AFB1 contamination and disease burden, and applies these insights to optimize monitoring strategies under resource constraints. Using official monitoring records of AFB1 and health risk data, our analysis estimated an average burden of 3.51 disability adjusted life years per 100,000 population across China. Interprovincial transfers of peanuts and peanut oil accounted for 52% more local disease burden than in-province production. By reallocating monitoring batches along these high-risk pathways, the optimized monitoring strategy reduced the national health burden by 25 percentage points relative to current monitoring. Beyond AFB1, our study provides a transferable framework for enhancing mycotoxin management in complex food systems, enabling policymakers to better protect public health under resource constraints.</p>