Mine ventilation resistance is a core factor affecting the safety and production efficiency of underground mining. Its scientific analysis and effective optimization are of great significance for ensuring mine safety production and improving the energy efficiency of ventilation systems. This paper adopts a combined approach of theoretical modeling and VentSim simulation to systematically investigate the composition characteristics of mine ventilation resistance and its influencing factors. Based on the Darcy-Weisbach equation and local resistance models, the calculation methods for frictional resistance and local resistance are derived, elucidating the influence mechanisms of roadway cross-sectional shape, wall roughness, and airflow velocity on ventilation resistance. Ventilation network solution theory is employed to analyze the coupling relationships among air quantity balance, pressure balance, and resistance distribution. Furthermore, a three-dimensional ventilation simulation model is developed using VentSim software to simulate airflow distribution and pressure variations in the ventilation system, and to validate the theoretical calculation results. The results show that the overall error between theoretical calculations and simulation results is controlled within 5%. However, in regions with small cross-sections or complex structures, the simulation results better reflect the actual nonlinear flow characteristics; for example, in a local narrow section of the 19 roadway, the simulated velocity reaches 9.1 m/s, representing an 18% deviation from the theoretical value. On this basis, six optimization measures are proposed: reducing the frictional resistance coefficient, rationally regulating air quantity, enlarging roadway cross-sectional area, shortening ventilation paths, optimizing roadway cross-sectional shape (preferably circular or arched), and improving local structures (e.g., using rounded transitions). Engineering applications demonstrate that comprehensive implementation of these strategies can improve ventilation system energy efficiency by approximately 19% - 27%, providing reliable theoretical support and practical reference for the design and dynamic optimization of mine ventilation systems.