Abstract This study investigates the theoretical and experimental aspects of the vibro-acoustic characteristics of cylindrical shells with internal substructures. On the theoretical side, a hybrid calculation method is proposed, which combines the condensed transfer function method with the direct stiffness method and the precise transfer matrix method. The cylindrical shell with internal substructures is decoupled, and the governing equations for the cylindrical shell substructure and the internal substructure are separately established. Furthermore, the coupling forces between the cylindrical shell substructure and the plate substructure are solved based on the condensed transfer function method. These coupling forces are then incorporated into the overall transfer equation of the cylindrical shell to obtain the vibro-acoustic response of the coupled structure. Compared with the finite element calculation results, the validity of the calculation method in this paper is verified. In terms of experiments, the natural frequency, mode and vibration acoustic response of the model were tested, and compared with the theoretical results, which was in good agreement. The study demonstrates that the proposed hybrid calculation method based on the condensed transfer function is effective in predicting the vibro-acoustic characteristics of cylindrical shells with internal substructures.