Exocrine pancreatic insufficiency (EPI) is a major cause of maldigestion and malnutrition, resulting from primary pancreatic diseases or other conditions. As the prevalence of EPI continues to rise, accurate identification of its etiology has become critical for the diagnosis and treatment of pancreatic secretory insufficiency. EPI can result from both pancreatic and non-pancreatic disorders. Pancreatic disorders include acute and chronic pancreatitis, pancreatic tumors, cystic fibrosis, procedures that involve pancreatic resection, and other rare causes. Non-pancreatic disorders of EPI include diabetes mellitus, celiac disease, inflammatory bowel disease, gastrointestinal and esophagectomy surgery, as well as advanced patient age. This review aims to provide a comprehensive analysis of the literature on EPI etiology, with a thorough overview to support its consideration as a potential diagnosis.