This thesis explores the role of immunotherapy in gastrointestinal malignancies, including colorectal, liver, esophageal, pancreatic, and gastric cancers. It outlines key immunotherapeutic strategies such as immune checkpoint inhibitors, cancer vaccines, adoptive cell therapy, and oncolytic virotherapy, while also contrasting them with the limitations of conventional treatments like chemotherapy, radiation, and targeted therapy. The thesis highlights clinical trial evidence, FDA-approved agents, and emerging approaches in different GI cancers. A major emphasis is placed on resistance mechanisms within the tumor microenvironment and the development of combination therapies to overcome them. Lastly, the thesis mentions the challenges of tumor heterogeneity and patient selection, while emphasizing the promise of next-generation immunotherapies and personalized treatment strategies.