A comprehensive three-dimensional dynamic model of a multi-cable double-drum winding hoister with flexible guides is presented, as the existing models cannot deal with the three-dimensional eccentricity of the cage and out-of-plane excitation generated by rotational drums. The entire system consists of three subsystems: cable subsystem, cage subsystem, and guide subsystem, respectively. Displacement and force boundary conditions are employed to couple those subsystems, and the interaction between cage and guides is considered as bidirectional coupling. The dynamic models of the three subsystems are established by Hamilton principle and Newton-Euler equation in a three-dimensional space independently. The dynamic model is discretized and solved by the Galerkin method and Runge–Kutta method. The three-dimensional displacement excitations and three-dimensional eccentricity can be handled in this dynamic model. The differences between two-dimensional dynamic model and three-dimensional dynamic model are discussed and the mechanism of entire system vibration are also analyzed by numerical simulation with typical unbalance factors, the cage eccentricity. The results show that the proposed three-dimensional dynamic model is more accurate in some realistic cases, existing out-of-plane excitation or three-dimensional eccentricity of the cage.