Background <p>Pembrolizumab plus lenvatinib is a standard first-line treatment option for advanced renal cell carcinoma (RCC), but data focused on patients aged ≥ 75 years remain limited. We evaluated the efficacy, safety, and treatment feasibility of this regimen in a Japanese multicenter cohort.</p> Methods <p>We retrospectively analyzed 170 patients with metastatic or unresectable RCC treated with first-line pembrolizumab plus lenvatinib. We compared those aged ≥ 75 years (<i>n</i> = 31) with those aged &lt; 75 years (<i>n</i> = 139), assessing treatment exposure, treatment modifications, adverse events (AEs), best overall response, progression-free survival and overall survival.</p> Results <p>The older patients more commonly received a reduced starting dose of lenvatinib (<i>P</i> = 0.02) and schedule modification (19% vs. 6%, <i>P</i> = 0.03). However, the number of lenvatinib dose reductions, final lenvatinib dose, and treatment duration were similar between the groups. There was no significant difference in any-grade AEs, grade ≥ 3 AEs, corticosteroid use for immune-related AEs, or AE-related treatment discontinuation. The objective response rate was 77% in patients aged ≥ 75 years and 65% in those aged &lt; 75 years (<i>P</i> = 0.20). Progression-free survival and overall survival were also comparable (<i>P</i> = 0.92 and <i>P</i> = 0.58, respectively), and age ≥ 75 years was not associated with progression-free survival or overall survival in multivariable analysis.</p> Conclusions <p>Our results suggest that pembrolizumab plus lenvatinib can be feasibly administered to selected patients aged ≥ 75 years through individualized dose attenuation and schedule modification without an apparent loss of efficacy or increase in severe toxicity.</p>