The design of selective and stable catalysts is a major challenge in heterogeneous catalysis, also true for propane dehydrogenation (PDH), an on-purpose route to produce propylene. Identifying nonprecious catalysts to replace Pt used today is another formidable task. Herein, we combine kinetic simulations, high-throughput computations, machine-learning concepts, and experiments to illustrate the key parameters controlling the performance of metallic catalysts in PDH. Our decision map successfully identifies NiMo as a very promising nonprecious metal catalyst, which is experimentally proven to outperform Pt in PDH. Our framework not only validates experimentally known catalysts but also provides ways for PDH catalyst engineering from theoretical high-throughput screening. We believe that the other 11 identified candidates will initiate further state-of-the-art experimental investigations and add important insights into the industrial development of catalysts for alkane dehydrogenation.