Milling of thin-walled aerospace structures is a critical and challenging process. Available models for the prediction of the effect of the fixture on the dynamic response of flexible workpieces are computationally demanding and fail to represent practical cases for milling of thin-walled structures. Based on the analysis of typical structural components encountered in the aerospace industry, a generalized unit-element, with the shape of an asymmetric pocket, was identified to represent the dynamic response of these components. Accordingly, a computationally efficient dynamic model was developed to predict the dynamic response of typical thin-walled aerospace structures using the Rayleigh–Ritz method. In the formulation of this model, the dynamics of a 3D pocket is represented by an equivalent 2D multispan plate taking into account the effect of deformable fixture supports. The developed model was validated numerically and experimentally for different workpiece geometries and various types of loading. This model resulted in one to two orders of magnitude reduction in computation time when compared with the finite element models, with prediction errors less than 10%. The developed model meets the conflicting requirements of prediction accuracy and computational efficiency needed for interactive fixture design.