In aircraft structural design, panel structures often bear enormous pressurized loads. To explore the optimal layout of aircraft panel structures under pressurized loads, this paper employs a hierarchical optimization method divided into three levels: (1) Topology optimization to determine the optimal number and position of longitudinal frames; (2) Size optimization to define intermediate parameters of the panel structure; (3) Stability criterion optimization to determine the optimal number and position of transverse frames. Taking a specific pressurized flat panel as the research object, this study first obtains a reasonable structural layout through topology optimization. Based on this layout, an engineering design plan is developed according to actual design requirements, followed by further refinement using advanced size optimization tools. The final detailed design dimensions are obtained to achieve the lightest possible structure.