This study presents a comprehensive, statistically validated comparison between a quantum-inspired optimization algorithm and classical simulated annealing for radiotherapy dose planning. Using a synthetic phantom, the quantum-inspired method demonstrated substantial improvements in target coverage (PTV D95: +123.4%) and dose homogeneity compared to classical SA, with strong statistical significance (p < 0.000001, Cohen’s d = 0.431). The research provides mechanistic insights into the algorithm’s superior ability to escape local minima and maintain exploration-exploitation balance, highlighting its potential for clinical application and guiding future developments in medical physics optimization.