Objectives To associate the early change in DL-CT parameters and HU with survival outcomes and treatment response in patients with metastatic renal cell carcinoma (mRCC). Methods DL-CT scans were performed at baseline and after 1 month of checkpoint immunotherapy or tyrosine kinase inhibitor therapy. Scans were reconstructed to conventional CT and DL-CT series, and used for assessment of HU, iodine concentration (IC), and the effective atomic number (Z(effective)) in the combined RECISTv.1.1 target lesions. The relative changes, defined as Delta IC(combined), Delta Z(effective)(combined), and Delta HU(combined), were associated with progression-free survival (PFS), overall survival (OS), and objective response rate (ORR). The reduction in the sum of diameters of target lesions >= 30% after 1 month was associated with OS, PFS, and ORR. Results Overall, 115 and 104 mRCC patients were included at baseline and 1 month, respectively. Median IC(combined) decreased from 2.3 to 1.2 mg/ml (p < 0.001), Z(effective)(combined) from 8.5 to 8.0 (p < 0.001), and HU(combined) from 86.0 to 64.00 HU (p < 0.001). After multivariate adjustments, the largest reductions in Delta IC(combined) (HR 0.47, 95% CI: 0.24-0.94, p = 0.033) and Delta Z(effective)(combined) (HR = 0.43, 95% CI: 0.21-0.87, p = 0.019) were associated with favorable OS; the largest reduction in Delta Z(effective)(combined) was associated with higher response (OR = 2.79, 95% CI: 1.12-6.94, p = 0.027). The largest reduction in Delta HU(combined) was solely associated with OS in univariate analysis (HR 0.45, 95% CI: 0.23-0.91). Reduction in SOD >= 30% at 1 month was not associated with outcomes (p > 0.075). Conclusions Early reductions at 1 month in Delta IC(combined) and Delta Z(effective)(combined) are associated with favorable outcomes in patients with mRCC. This information may reassure physicians and patients about treatment strategy.