The National Cancer Institute's Clinical Trials and Translational Research Advisory Committee (CTAC) Gastric and Esophageal Cancers Working Group, convened in December 2021, provided recommendations to advance research on gastric and esophageal cancers. These cancers are among the leading causes of cancer mortality globally, with significant morbidity and mortality in the U.S. Despite advances in cancer science, survival rates remain low, highlighting the need for further progress. The Working Group emphasized the importance of translational research to bridge fundamental discoveries with clinical applications. The Working Group recommended building a robust pipeline of translational opportunities by strengthening key enabling resources and tools. This includes developing biospecimen repositories with well-characterized samples, improving research tools such as model systems, laboratory analytic methods, and computational methods, and advancing future research directions in biological insights, treatment, and prevention. Specific recommendations included creating a centralized biospecimen repository with standardized collection and processing methods, developing more robust model systems like organoids, and enhancing computational methods for data analysis. The Working Group also emphasized the need for improved clinical assessment tools and therapeutic regimens, as well as the development of novel preventive interventions. In terms of future research, the Working Group highlighted the importance of understanding the biological mechanisms of gastric and esophageal cancers, improving treatment strategies, and developing effective prevention methods. They recommended applying multi-omics and model systems to enhance screening, detection, and surveillance, and to identify new biomarkers and interventions. The Working Group also stressed the importance of interdisciplinary collaboration and the need for standardized methods in data collection and analysis to ensure the feasibility and validity of research findings. Overall, the recommendations aim to improve the prevention, diagnosis, and treatment of gastric and esophageal cancers through a comprehensive and integrated approach.The National Cancer Institute's Clinical Trials and Translational Research Advisory Committee (CTAC) Gastric and Esophageal Cancers Working Group, convened in December 2021, provided recommendations to advance research on gastric and esophageal cancers. These cancers are among the leading causes of cancer mortality globally, with significant morbidity and mortality in the U.S. Despite advances in cancer science, survival rates remain low, highlighting the need for further progress. The Working Group emphasized the importance of translational research to bridge fundamental discoveries with clinical applications. The Working Group recommended building a robust pipeline of translational opportunities by strengthening key enabling resources and tools. This includes developing biospecimen repositories with well-characterized samples, improving research tools such as model systems, laboratory analytic methods, and computational methods, and advancing future research directions in biological insights, treatment, and prevention. Specific recommendations included creating a centralized biospecimen repository with standardized collection and processing methods, developing more robust model systems like organoids, and enhancing computational methods for data analysis. The Working Group also emphasized the need for improved clinical assessment tools and therapeutic regimens, as well as the development of novel preventive interventions. In terms of future research, the Working Group highlighted the importance of understanding the biological mechanisms of gastric and esophageal cancers, improving treatment strategies, and developing effective prevention methods. They recommended applying multi-omics and model systems to enhance screening, detection, and surveillance, and to identify new biomarkers and interventions. The Working Group also stressed the importance of interdisciplinary collaboration and the need for standardized methods in data collection and analysis to ensure the feasibility and validity of research findings. Overall, the recommendations aim to improve the prevention, diagnosis, and treatment of gastric and esophageal cancers through a comprehensive and integrated approach.