We recently traveled to Denver, Colorado, for a State of the Science Summit on Gastrointestinal Malignancies, which featured insights from University of Colorado and Rocky Mountain Cancer Centers faculty. Meeting topics spanned the importance of molecular testing in the management of newly diagnosed metastatic colorectal cancer, advances with biomarker-directed therapies and immunotherapies in the relapsed/refractory setting, and the role of tumor sidedness in the treatment of the disease. Experts also highlighted novel approaches being explored in pancreatic cancer, data with immunotherapy in gastric and gastroesophageal junction cancer, and novel investigational agents in hepatocellular carcinoma.