Abstract Food safety monitoring faces the challenge of tackling multiple chemicals along the various stages of the food supply chain. Our study developed a methodology for optimizing sampling for monitoring multiple chemicals along the dairy supply chain. We used a mixed integer nonlinear programming approach to maximize the performance of the sampling in terms of reducing the risk of the potential disability adjusted life years (DALYs) in the population. Decision variables are the number of samples collected and analyzed at each stage of the food chain (feed mills, dairy farms, milk trucks, and dairy processing plants) for each chemical, given a predefined budget. The model was applied to the case of monitoring for aflatoxin B 1 /M 1 (AFB 1 /M 1 ) and dioxins in a hypothetical Dutch dairy supply chain, and results were calculated for various contamination scenarios defined in terms of contamination fraction and concentrations. Considering various monitoring budgets for both chemicals, monitoring for AFB 1 /M 1 showed to be more effective than for dioxins in most of the considered scenarios, because AFB 1 /M 1 could result into more DALYs than dioxins when both chemicals are in same contamination fraction, and costs for analyzing one AFB 1 /M 1 sample are lower than for one dioxins sample. The results suggest that relatively more resources be spent on monitoring AFB 1 /M 1 when both chemicals’ contamination fractions are low; when both contamination fractions are higher, relatively more budget should be addressed to monitoring dioxins.