Flywheels are widely used on-board spacecraft for attitude control or energy storage. However, micro-vibrations generated by flywheels will influence the performance of high-sensitivity instruments on-board the spacecraft. This study addresses the dynamic modeling and analysis of the micro-vibration isolation of flywheel assemblies. Firstly, an analytical model was developed to describe the coupled multiple flywheel system (MFS) and multi-axis isolation system, with equations in state-space form presented for control purposes. This analytical model properly reflects the mass and inertia properties, the gyroscopic effects and the flexible modes of the coupled system, which can be generalized for isolation applications when multiple flywheels are mounted together. Secondly, the analytical model was validated using the MSC.NASTRAN software based on finite element techniques. Finally, using the proposed model, we investigated the coupled dynamics of the MFS and the isolation system. The results show that the mass and inertial properties and the gyroscopic effects of the MFS will induce couplings between the structural modes. The gyroscopic effects of one flywheel interact with or counteract the effects of the others, which will produce complex vibrational modes and affect the isolation performance accordingly. Thus, the coupled dynamics within the system should receive attention during isolation design for the MFS.