Abstract Objectives To evaluate the effectiveness and safety of current treatment strategies for the vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic (VEXAS) syndrome. Methods A protocolized systematic review according to PRISMA guidelines was performed. Three databases were searched for reports on treatment strategies for VEXAS. Data from the included publications was extracted and a narrative synthesis was performed. Treatment response was recorded as complete (CR), partial (PR) or none (NR) depending on changes in clinical symptoms and laboratory parameters. Patient characteristics, safety data and previous treatments were analyzed. Results We identified 36 publications with a total of 116 patients, 113 (98.3%) were male. The identified reports included azacytidine (CR 9/36, 25%; PR 14/36, 38.9%), JAK inhibitors (CR 11/33, 33%; PR 9/33, 27.3%), tocilizumab (CR 3/15, 20%; PR 6/15, 40%), allogeneic stem cell transplantation (alloSCT) (CR 6/7, 85.7%; one patient died), anakinra (CR 4/5, 80%; NR 1/5, 20%), canakinumab (CR ½, 50%; PR ½, 50%) and glucocorticoid monotherapy (CR 1/6, 16.7%; PR 4/6, 66.7%). Individual reports were available for TNF-inhibitors, rituximab, and methotrexate. Data on adverse events were available for 67 patients (67/116, 57.8%) and included: pneumonia (12/67, 17.9%), other infections (9/67, 13.4%), venous thromboembolisms (VTE) (6/67, 8.9%), cytopenias (4/67, 6.7%), acute (4/67, 5.9%) and chronic graft-versus-host-disease (2/67, 2.9%). Conclusion Current data on VEXAS treatment are limited and inhomogeneous. Treatment decisions should be individualized. For the devolvement of treatment algorithms clinical trials are needed. AEs remain a challenge, especially an elevated risk for venous thromboembolism associated to JAKi treatment should be carefully considered.