Analysis and simulation of fluid–thermal–structure coupling play an essential role in hypersonic flight vehicle design. In this study, the spectral proper orthogonal decomposition (SPOD) method is employed to establish the reduced-order model (ROM) for a hypersonic panel with a thermal protection system. First, the subsystem of the aerothermoelastic (AETI) system is modeled. Specifically, the aerodynamic heating is calculated with Eckert’s reference enthalpy method. The heat transfer is carried out with the finite difference method, and the aeroelastic equation is built by integrating the von Kármán plate theory and the third-order piston theory. Additionally, the two-way coupling between aerothermal and aeroelastic subsystems is used to construct the AETI system. Second, the optimal snapshots with the resultant local SPOD modes (SPOMs) are evaluated in terms of accuracy. Third, the global SPOMs for variable flight parameters are promoted to develop the robustness of the proposed SPOD/ROM. The findings indicate that taking the transient chaotic response as snapshots can produce global SPOMs. SPOD/ROM for the present AETI system improves the efficiency by 10–50 times compared to the classic Galerkin method. Moreover, the global SPOMs to variable Mach number and flight altitude are essentially the natural modes of the AETI panel, and thus are dependent on the temperature of the fluttering panel, which is our new finding in the present study. Overall, the current research will provide methods for accurately and efficiently predicting thermal loads, flutter boundary, and dynamic response for hypersonic flight vehicles.