The approach to design compressor blades has been transformed over the years by the advent of efficient numerical optimization algorithms and increasing computing power. This has allowed designers to focus on finding the best optimization methodology for a desired application. However, transonic flow conditions on compressor blades still present considerable modeling and optimization challenges, making the optimization of even a 2D blade section a non-trivial undertaking. This paper then focuses on the design of a new state-of-the-art transonic compressor cascade for future wind tunnel test campaigns at the DLR. For this purpose, a thorough review was performed of similar cascades previously tested at the DLR’s Transonic Cascade Wind Tunnel. From this review, a main reference was picked corresponding to a modern cascade with notably good efficiency at high aerodynamic loading. The data gathered informed the definition of the optimization’s design strategy applied with the DLR’s in-house optimizer, AutoOpti. The process chain was evaluated with the DLR’s CFD solver for turbomachinery applications, TRACE, by performing RANS simulations with the k-ω SST turbulence model and γ-ReΘ transition model. The optimization was set to minimize two separate objective functions: the first one focused on the efficiency at the aerodynamic design point, while the second one was focused on the efficiency over the cascade’s working range. The result is a Pareto front of cascades with a wide variety of design characteristics and a considerable improvement in efficiency over the working range of about 24%. This improvement was achieved while maintaining a similar aerodynamic blade loading, quantified by a maximum increase of 3% of the de Haller number. Further post-optimization analyses were performed to select the “best” cascade for future wind tunnel test campaigns. The significant improvements obtained with respect to the reference and with a wide variety of cascade designs demonstrates that there is still much to be learned about blade design through optimization; even for 2D cascades and specially in transonic flow conditions.