Globally, early detection and interception of gastric cancer remains limited by the lack of a broad screening paradigm for individuals with the exception of those at established hereditary risk (e.g., hereditary diffuse gastric cancer or CDH1 germline mutation status). The path forward will likely rely on establishment of biomarkers using multiple -omic approaches to detect molecular profiles associated with gastric cancer risk that can in turn be leveraged to identify individuals who may benefit from more intensive evaluation, such as screening endoscopy. In this issue, Shu and colleagues describe the results of a case-control cohort study of Asian individuals that demonstrates baseline metabolite levels are predictive of future gastric cancer risk above and beyond lifestyle and demographic risk factors. We discuss the promise and limitations of these exemplar circulating biomarkers and emphasize the need for a multifactorial risk assessment to advance precision prevention and early detection of gastric cancer.See related article by Shu et al., p. 1634.