Whereas, the later process requires two reactors: one to convert EtOH to AcH and the other to transform a mixture of EtOH and previously produced AcH into BD. Both of the processes, however, follow the generally accepted mechanism referred to as the Toussaint-Kagan pathway as shown in Scheme 1. Since the first catalyst system, Al2O3/ZnO, developed by Lebedev in the 1930s, a myriad of catalysts have been proposed by many researchers. These catalysts are predominantly based on mixed or supported oxides of early-to-late transition metal and lanthanide elements. In this study, we explored multi-element catalysts comprising up to 14 elements co-supported on mesoporous silica by means of GA-driven HTE. This approach allowed us to comprehensively address the complex ETB reaction pathway, where individual reactions are expected to be promoted by catalytic sites with varying natures. This study involve the following steps: designing multi-element catalysts suitable to enhance the BD yield and selectivity, evaluating the prepared catalysts using an in-house designed HTE instrument, using the GA to evolve the catalysts based on the BD yields, and utilizing ML algorithms to extract catalytic trends from the obtained dataset. Scheme 1. Toussaint-Kagan pathway for EtOH to BD conversion.