Background: Although not officially approved, salvage nivolumab plus ipilimumab (nivo/ipi) treatment after prior PD-1/PD-L1 immune checkpoint inhibition is frequently used in metastatic renal cell carcinoma (mRCC). However, very limited data are available to guide such therapy. Methods: A search in Medline database and conference abstracts published in English before September 1, 2020 yielded 4 studies reporting salvage nivo/ipi outcomes of mRCC patients. We added additional information from 27 mRCC patients who received salvage nivo/ipi at The Ohio State University after prior PD-1 pathway inhibition. Hence, we performed a meta-analysis of five studies to further characterize the safety and efficacy of salvage nivo/ipi treatment. Results: Among 155 patients with measurable treatment response, we found that salvage nivo/ipi had an objective response rate of 19% (95% CI, 0.13-0.25), which was significantly lower than response to prior PD-1/PD-L1 inhibition (odds ratio, 0.35, 95% CI, 0.18-0.67; p < 0.01). Response to prior PD-1/PD-L1 inhibition did not correlate with salvage nivo/ipi response (odds ratio, 1.41, 95% CI, 0.51-3.87; p = 0.51). Additionally, salvage nivo/ipi was associated with 26% (95% CI, 0.19-0.33) grade ≥ 3 adverse events, which was lower than the toxicity in the upfront setting reported in Checkmate-214 trial. Conclusions: It is feasible to have salvage nivo/ipi treatment in mRCC. Salvage nivo/ipi treatment has a lower efficacy and lower toxicity compared with its use in the first-line setting.