Vasculitis involving the gastrointestinal (GI) tract typically occurs in association with multisystem disease. Isolated superior mesenteric artery (SMA) vasculitis is a rare disorder that has a high degree of morbidity and mortality. Patients often present with nonspecific symptoms, and this condition can lead to varying degrees of intestinal ischemia, significant gastrointestinal bleeding, and bowel infarction, leading to perforation, peritonitis, and sepsis from bacterial translocation. Diagnosing this condition can be very challenging. High clinical suspicion and early diagnosis using both laboratory workup and appropriate vascular imaging are pivotal in improving outcomes in such patients. Herein, we describe the case of isolated yet multifocal SMA vasculitis with coexisting superior mesenteric vein (SMV) thrombosis. Medical therapy alone resulted in clinical and radiographic improvements. To our knowledge, there have not been any previous reports of this unique coexistence.