A common multidisciplinary design optimization (MDO) task for aircraft is their aero-structural design. In this task, the shape and structure sizing of the aircraft are modified concurrently. A large parameter space necessitates gradient-based approaches where accurate gradients of all involved disciplines are needed to find the optimal design of the system. It was shown that CFRP laminate tailoring is already able to modify the structure design to increase the performance of commercial transport aircraft configurations. With growing interest in flexible, high aspect ratio wings, where the structure design is expected to have a larger impact on the aircraft performance, this technology shows a lot of potential. The MDO suite Lagrange, developed at Airbus Defence and Space, is coupled to DLR’s computational fluid dynamics (CFD) code, TAU, within the high-performance computing (HPC) software integration framework FlowSimulator to accurately predict the aircraft performance. The usage of direct high-fidelity methods for structure sizing and aircraft hull shape sensitivity calculation is prohibitively expensive for the number of design variables occurring in industry relevant optimization problems. The adjoint method remains the only feasible method for cruise performance gradient calculation. To reflect aircraft industry requirements, the loads process engages a high number of load cases that prevents the usage of high-fidelity CFD. Therefore, a linear aerodynamics model is coupled to the structure solver for the loads and sizing process. This enables the structural analysis in an optimization process without compromising the number of constraints and load cases. This paper applies different laminate parametrizations including isotropic layups as well as balanced and symmetric layups to evaluate their influence on the design task. Furthermore, a model is optimized with a frozen ply-share determined in the sizing process and the overall thickness of the laminate exposed to the performance optimization. The optimization scenario chosen is a civil transport aircraft configuration with strong performance and structure interaction, the DLR F25. This work is carried out collaboratively by DLR and Airbus Defence and Space as part of a research fellow sponsorship. Development of DLR-F25 was funded by the German Federal Ministry for Economic Affairs and Climate Action.