Kikuchi-Fujimoto disease (KFD) is an acute febrile disease that mainly involves histiocytic necrotizing lymphadenitis in children and young adults. Diagnosis of KFD is even more difficult if image-guided percutaneous biopsy is technically challenging. We present a case of clinically diagnosed KFD in an 11-year-old boy who presented with fever, abdominal pain, and mesenteric lymphadenopathy, resulting in a diagnostic challenge. Additionally, we conducted a systematic review, and our goal was to describe the spectrum of disease, therapy, and outcomes. We identified 15 cases of KFD with symptoms that mimicked mesenteric lymphadenitis. Reports from the Americas, Europe, and Asia were also included. Most patients were male, exhibited leukopenia and elevated inflammatory markers, and recovered without significant sequelae or complications. A high index of suspicion of KFD should be maintained in children presenting with prolonged fever and unusual manifestations, such as mesenteric lymphadenitis.