The load resulting from the explosion of a missile warhead comprises high-intensity shock waves and a random distribution of fragment loads characterized by diverse shapes, sizes, and distributions. Complex coupling between shock waves and fragments are necessary to comprehensively evaluate the blast-resistance performance of U-typed sandwich panels. A numerical model based on the finite-element software was established to investigate the dynamic response of U-typed sandwich-panel structures under the combined action of shock waves and randomly distributed fragment groups. The effectiveness of the numerical model was validated by comparing results with experimental values. A random fragment field-generation model that conforms to the characteristics of a power-law distribution is constructed through the implementation of the Voronoi segmentation algorithm and a Python-based computational module. Building on this framework, this study explored the complex coupling process between shock waves and randomly distributed fragments. Furthermore, an in-depth analysis was performed to examine the structural damage characteristics with various fragment distributions and fragment densities. Diverse perforation patterns were observed in the upper plate of the U-typed sandwich panel for different fragment densities. Furthermore, the perforation area of the upper plate initially increased, followed by a decrease with increasing fragment density.