This article provides a materials selection methodology applicable to lightweight actively cooled panels, particularly suitable for the most demanding aerospace applications. The key ingredient is the development of a code that can be used to establish the capabilities and deficiencies of existing panel designs and direct the development of advanced materials. The code is illustrated for a fuel-cooled combustor liner of a hypersonic vehicle, optimized for minimum weight subject to four primary design constraints (on stress, temperatures, and pressure drop). Failure maps are presented for a number of candidate high-temperature metallic alloys and ceramic composites, allowing direct comparison of their thermostructural performance. Results for a Mach 7 vehicle under steady-state flight conditions and stoichiometric fuel combustion reveal that, while C–SiC satisfies the design requirements at minimum weight, the Nb alloy Cb752 and the Ni alloy Inconel X-750 are also viable candidates, albeit at about twice the weight. Under the most severe heat loads (arising from heat spikes in the combustor), only Cb752 remains viable. This result, combined with robustness benefits and fabrication facility, emphasizes the potential of this alloy for scramjets.