Background: Sickle cell disease is the leading etiology for atraumatic humeral head avascular necrosis worldwide. Treatment of this condition is not standardized, with only few studies evaluating clinical outcomes after surgical interventions. The aim of this study was to review the available evidence on the results of surgical intervention for humeral head avascular necrosis in the sickle cell disease population. Methods: A systematic electronic search was conducted using PubMed (MEDLINE), EMBASE, and Cochrane Library databases. Relevant studies that reported the outcomes of surgical intervention for humeral head avascular necrosis for patients with sickle cell disease were reviewed. Outcome parameters were pain, range of motion, specific shoulder outcome scores, and complications. Results: Six studies, three retrospective cohorts (2 level III and 1 level IV) and three case series (level IV), were included in this review. A total of forty-three patients with sickle cell disease, comprising forty-nine shoulders, underwent different surgical procedures. Surgical procedures were core decompression, arthroscopic intervention, humeral head resurfacing, shoulder hemiarthroplasty, and total shoulder arthroplasty. Conclusion: Surgical intervention for humeral head avascular necrosis in patients with sickle cell disease is selected based on the osteonecrosis stage. In the precollapse stage, core decompression is regarded as the first surgical option. However, in the light of current evidence, it has not been confirmed to prevent or delay natural progression of the disease. Shoulder arthroplasty is reserved for late stages, which despite the fairly good outcomes, data for long-term implant survival and complications are not well documented.