The presence of an acute abdomen is a common presentation among cancer patients and could also be the initial presentation of an underlying abdominal malignancy. Currently, advances in cancer diagnosis and treatment often extend survival; therefore there is a high likelihood that patients will have a complication related to cancer care. Approximately 40% of cancer patients present to the emergency department with gastrointestinal symptoms. These presentations can stem from the underlying malignancy, cancer-related medications, or the spectrum of pathologies present in healthy patients. Evaluation of immunosuppressed patients can be deceptive since normal clinical signs may be diminished by neutropenia or steroid administration. Management decisions should be made after consideration of multiple factors including disease burden, prognosis, quality of life, and patient desires. This chapter focuses specifically on immunosuppressed patients who present with an acute abdomen and the differential diagnosis, presentation, and management of each of these pathologies.