The design of compressor blades has been transformed by the advent of optimization algorithms, allowing designers to focus on finding the best optimization strategy for a desired application. However, transonic flow conditions on compressor blades still present considerable modeling challenges, even for a 2D blade section. This paper then focuses on the design of a new state-of-the-art compressor cascade for future test campaigns at the DLR’s Transonic Cascade Wind Tunnel (TGK). For this purpose, a review of the cascades previously tested at the TGK was performed to select a main reference with good efficiency at high loading. The data gathered also informed the optimization strategy applied with the DLR’s optimizer, AutoOpti. The process chain was evaluated with Reynolds Averaged Navier–Stokes CFD simulations using the DLR’s solver, TRACE. The optimization was set to minimize two objective functions: the first one focused on the efficiency at the design point, and the second one focused on the efficiency over the working range. The result is a Pareto front of cascades with a wide variety of design features with an efficiency improvement over the working range of about 24%. This improvement was achieved with a comparable aerodynamic loading. Further analyses were performed to select the “best” cascade for future test campaigns. The significant improvement obtained with respect to the reference and the wide variety of designs observed demonstrates that there is still much to be learned about blade design through optimization; even for 2D cascades and specially in transonic flow.