The incidence of metastatic bone disease is increasing, and the humerus is the second-most affected long bone. Metastatic disease of the humeral diaphysis is a significant cause of morbidity, leading to pain, loss of function, and diminished quality of life. Management depends on factors such as tumor histology, lesion characteristics, fracture displacement, and patient function. While nonoperative measures including radiation therapy and systemic treatments can relieve symptoms in select cases, impending or completed fractures frequently require surgical intervention. Surgical options include curettage with cement packing, intramedullary nailing, plate fixation, and resection with reconstruction. The goal of surgery is to provide durable fixation, restore function, and allow early mobilization while minimizing complications. This chapter explores the epidemiology, indications, and surgical strategies for diaphyseal humeral metastases, emphasizing an individualized approach to optimize patient outcomes.