Gastrointestinal (GI) malignancies are some of the most common and devastating malignancies and include colorectal, gastric, esophageal, hepatocellular, and pancreatic carcinomas, among others. Five-year survival rates for many of these malignancies remain low. The majority presents at an advanced stage with limited treatment options and poor overall survival. Treatment is advancing but not at the same speed as other malignancies. Chemotherapy and radiation treatments are still only partially effective in GI malignancies and cause significant side effects. Thus, there is an urgent need for novel strategies in the treatment of GI malignancies. Recently, immunotherapy and checkpoint inhibitors have entered as potential new therapeutic options for patients, and thus, cancer vaccines may play a major role in the future of treatment for these malignancies. Further advances in understanding the interaction between the tumor and immune system have led to the development of novel agents, such as cancer vaccines.