To enhance the comprehensive performance of artillery internal ballistics-encompassing power, accuracy, and service life-this study proposed a multi-stage multidisciplinary design optimization (MS-MDO) method. First, the comprehensive artillery internal ballistic dynamics (AIBD) model, based on propellant combustion, rotation band engraving, projectile axial motion, and rifling wear models, was established and validated. This model was systematically decomposed into subsystems from a system engineering perspective. The study then detailed the MS-MDO methodology, which included Stage I (MDO stage) employing an improved collaborative optimization method for consistent design variables, and Stage II (Performance Optimization) focusing on the independent optimization of local design variables and performance metrics. The methodology was applied to the AIBD problem. Results demonstrated that the MS-MDO method in Stage I effectively reduced iteration and evaluation counts, thereby accelerating system-level convergence. Meanwhile, Stage II optimization markedly enhanced overall performance. These comprehensive evaluation results affirmed the effectiveness of the MS-MDO method.