Objective Assess the suitability of high-resolution metabolomics (HRM) for measure of internal exposure and effect biomarkers from deployment related environmental hazards. Methods HRM provides extensive coverage of metabolism and data relevant to a broad spectrum of environmental exposures. This review briefly describes the analytic platform, workflow and recent applications of HRM as a prototype environmental exposure surveillance system. Results Building upon techniques available for contemporary occupational medicine and exposure sciences, HRM methods are able to integrate external exposures, internal body burden of environmental agents and relevant biological responses with health outcomes. Conclusions Systematic analysis of existing Department of Defense Serum Repository samples will provide a high-quality cross-sectional reference dataset for deployment-associated exposures while at the same time establishing a foundation for precision medicine.