The PrandtlPlane (PrP) aircraft wing-box least-weight design is presented in this work. This design problem is formulated as a constrained non-linear programming problem (CNLPP), by integrating static, buckling, fatigue and manufacturability requirements, under different loading conditions. The solution search is carried out by means of a suitable multi-scale optimisation (MSO) approach. The physical responses involved into the CNLPP formulation are evaluated at the wing-box architecture level (macroscopic scale) and at the stiffened panel level (component scale), as well. The scale transition is ensured by means of a suitable global-local (GL) modelling approach, while the CNLPP is solved by means of an in-house genetic algorithm. The effectiveness of the proposed approach is tested on the PrP wing-box structure, but the presented strategy can be easily extended to conventional aircraft wings.