Background and Objectives: Estimating the environmental and occupational burden of disease aims to compare and rank environmental and occupational risk factors based on their impact on health, with a view to guiding public policies and prevention strategies in the fields of environmental health and occupational health. This approach requires identifying and prioritizing the disease-risk factor pairs of interest on which to base the estimation of this burden. This report presents the prioritization method applied by Santé publique France and the list of prioritized pairs to conduct an initial estimation of the environmental and occupational burden of disease in France. Method: The first step of this work consisted of prioritizing diseases and injuries based on their contribution to the total disease burden. The second step consisted of prioritizing environmental and occupational risk factors according to their impact on the burden of the previously prioritized diseases and injuries. These two steps were based on a comparative analysis of the most recent and comprehensive national burden of disease estimates currently available for France. These estimates were produced, respectively, as part of the international Global Burden of Disease (GBD) project of the Institute for Health Metrics and Evaluation (IHME) and the Global Health Estimates (GHE) project of the World Health Organization (WHO). The comparisons were based on various health burden indicators: DALYs (Disability-Adjusted Life Years), YLL (Years of Life Lost), and YLD (Years Lived with Disability), as well as on attributable risk fractions (ARF) measuring the respective impact of exposure to various environmental or occupational risk factors on the occurrence of diseases or injuries. Results: Following these two steps, nine disease-environmental or occupational risk factor pairs were prioritized. Three pairs concern cancers of the trachea, bronchi, and lung, linked to occupational exposure to asbestos, exposure to ambient particulate matter pollution, or residential radon. Two pairs relate to ischemic heart disease, linked to exposure to ambient particulate matter pollution or low temperatures. Two pairs concern strokes, linked to exposure to low temperatures or ambient particulate matter pollution. The last two pairs focus on low back pain linked to exposure to ergonomic risk factors and accidental falls linked to occupational accidents. Discussion: The prioritization method used enabled the establishment of a shortlist of disease-risk factor pairs on which to conduct an initial estimate of the environmental and occupational burden of disease in France. The prioritized pairs are consistent with those documented in the scientific literature. Furthermore, this study highlighted the main limitations associated with each of the two data sources used (GBD vs. GHE). To improve the accuracy of the estimates produced for France, it is necessary to adapt the IHME and WHO estimation methods to the French context and to use the most robust and relevant health, environmental, and occupational data available at the national level. Failing that, new data will need to be generated in order to comprehensively estimate the environmental impact on health. Generating such data is, however, a lengthy and complex process and requires, as a first step, narrowing the scope of the investigation to only the prioritized pairs. Outlook: The next phase of this project will aim to assess the feasibility of estimating the burden associated with each of these pairs using nationally available health, environmental, and occupational data, and to guide future work by Santé publique France toward acquiring new input data. More broadly, this initial work will serve as a foundation for guiding the agency’s future research on the environmental and occupational burden of disease in France.