Background/objective: Older adults experience a disproportionate burden of severe influenza. In the P303 trial (NCT058279789), mRNA-1010 showed greater immunogenicity versus high-dose inactivated influenza vaccine (HD-IIV4) in adults ≥65 years of age. Here, we used a correlate-of-protection framework to estimate the relative VE (rVE) of mRNA-1010 compared with HD-IIV4. Methods: A sigmoidal function was used to model the relationship between geometric mean haemagglutinin assay inhibition (HAI) titers (GMTs) and vaccine efficacy (VE) using data from the P304 trial (NCT06602024), which compared mRNA-1010 and the standard-dose IIV4 in adults ≥50 years of age. The model was then applied to GMTs from the P303 trial to estimate rVE of mRNA-1010 vs. HD-IIV4 in adults ≥65 years. Temporal waning and weighting of case distributions were incorporated to provide a season-integrated estimate. Simulations were performed for three influenza seasons (A/H1N1-dominant, A/H3N2-dominant, and balanced), with a sensitivity analysis varying vaccination and epidemic peak timing. Results: At Day 29, rVE for mRNA-1010 vs. HD-IIV4 was 24.1% (95% CI: 18.2–29.5%) against A/H1N1, 14.5% (8.3–20.3%) against A/H3N2, and 21.0% (16.0–25.8%) against B/Victoria. The season-integrated rVE was 12.4% (3.4–21.3%) across all three strains, with point estimates ranging from 11.6% to 12.6%. Similar findings were seen across simulated seasons, with rVE estimates ranging from 8.8% to 14.3% when varying vaccination timing, peak timing, and strain dominance. Conclusions: Based on this CoP framework, mRNA-1010 was projected to have higher VE than HD-IIV4 in adults ≥65 years of age across a range of simulated epidemiological conditions.