Lacking high-level evidences, the benefit of cytoreductive treatments in patients with metastatic renal cell carcinoma remains controversial. To investigate advantages and drawbacks, we performed a systematic review of the literature on the role of cytoreductive nephrectomy, surgical metastasectomy, and other metastases-directed therapies. A systematic search of the MEDLINE database was performed of all studies reporting on these topics: out of the 791 identified articles, 49 studies were finally included in our evidence synthesis. Combining cytoreductive nephrectomy with targeted therapy improves survival compared to systemic treatments alone. Renal tumors more commonly spread to the lungs (50–60%), bones (30–40%), and lymph nodes (20–40%), although almost every organ can be involved. Both number of metastases and metastatic sites affect prognosis: complete resection of all tumor deposits is associated with lower risk of mortality, regardless of performance status. All local treatments are associated with a non-negligible morbidity and mortality, and a careful selection of patients is mandatory, based on performance status, cancer burden, site, and number of metastases. Palliative metastasectomy may help controlling cancer-related symptoms in patients with a poor prognosis but only a complete extirpation of the primary tumor, and all secondary deposits could improve survival and defer systemic treatments toxicity.