Cyclone preheaters are widely employed in cement and process industries for heat recovery; however, internal erosion from particle-laden flows significantly reduces component life and increases maintenance costs. This study presents an integrated CFD–statistical–experimental approach to minimize erosion through geometric optimization. Five cyclone geometries were analyzed in ANSYS Fluent using a k–ε turbulence model coupled with a discrete-phase erosion model. A parametric study was conducted using main-effect analysis, regression, and ANOVA in Minitab to investigate the effects of inlet velocity, particle size, and flow rate on erosion, identifying key factors that influence it. The best-performing geometry (Design 2) was 3D-printed using PLA and tested in a closed sand–water loop, with observed wear patterns closely matching CFD predictions. Microscopic analysis confirmed mechanisms such as micro-cutting, ploughing, and crater formation in high-impact regions. Compared with the baseline, the optimized geometry reduced peak erosion rates by approximately 70%, demonstrating that targeted geometric modifications, particularly of inlet orientation and cone angle, offer a cost-effective strategy to enhance cyclone durability and operational efficiency.