Background: The role of cytoreductive nephrectomy (CNx) in patients with metastatic renal cell carcinoma (mRCC) is currently in question. Assessing the benefits and risks of CNx is challenging, with a lack of validated prognostic tools. Biomarkers of the systemic inflammatory response have prognostic utility in mRCC and are included in the IMDC score used to predict survival in patients with mRCC treated with systemic therapy. We sought to investigate their role in patients with mRCC who had undergone CNx. Methods: A cohort of 68 patients, suitable for first-line VEGFR inhibitor (VEGFRi) systemic therapy, who had undergone CNx for mRCC, were identified from a clinical database of patients referred to a regional mRCC service. Inflammatory biomarkers from routine blood tests (haemoglobin, white cell count, neutrophil count, platelets, C-reactive protein (CRP), albumin) and the IMDC score, measured at the time of diagnosis of mRCC, were recorded. The relationship between these and overall survival and time to VEGFRi (tVEGFRi) was examined using Kaplan-Meier and Cox-regression methods. Results: Data were available for 68 patients. Median survival was 33.7 months. On multivariate analysis, albumin ( < 35g g/dL v ≥35 g/dL) and CRP (≤ 10 mg/L v > 10 mg/L) were independently associated with overall survival (p = 0.027 and p = 0.034 respectively). Albumin stratified survival from 24.7 to 87.2 months (p < 0.0001) and CRP from 29.4 to 82.3 months (p = 0.004). 40 (59%) patients subsequently commenced VEGFRi therapy. Median tVEGFRi was 18.1 months, with only 5 (7%) patients commencing treatment within 3 months. 16 (24%) patients yet to receive systemic therapy remain alive after a median 54.0 months follow-up. On multivariate analysis, albumin was also predictive of tVEGFRi (p = 0.037), stratifying tVEGFRi from 6.07 to 45.7 months (p = 0.002). Conclusions: These results highlight that biomarkers of the systemic inflammatory response are strong prognostic factors in mRCC patients who have undergone CNx. Albumin and CRP, but not IMDC, predict survival in this patient group. Significantly, the population investigated here differ from those included in the CARMENA and SURTIME studies, with a majority undergoing surveillance prior to VEGFRi therapy. Our results support a role for CNx in patients where deferred systemic therapy strategies may be employed. Albumin may assist in clinical decision making when considering when to start systemic therapy. We advocate further studies to investigate the prognostic role of these simple, routine clinical tests in patients with mRCC undergoing CNx.