Myosin heavy chain 9 (MYH9), a non-muscle myosin heavy chain protein, has been identified as a significant factor in gastrointestinal (GI) oncology, with its overexpression in various GI malignancies such as esophageal, gastric, and colorectal cancers being associated with poor prognosis and playing a role in tumor invasion and metastasis. This comprehensive review synthesizes the current body of knowledge regarding MYH9's role in GI tumors, focusing on its molecular mechanisms, including its interaction with key signaling pathways like the phosphatidylinositol 3-kinase/protein kinase B/mechanistic target of rapamycin axis, which suggests a role in cancer cell survival, proliferation, and epithelial-mesenchymal transition. The review also explores MYH9's potential as a therapeutic target, with preclinical models demonstrating promising results in inhibiting tumor growth and enhancing chemosensitivity. The evidence suggests that MYH9 is a multifaceted protein with significant implications in GI tumor biology, warranting further research to elucidate its mechanisms of action and develop targeted therapies that could improve patient outcomes.