Recently, we took advantage of a mechanochemical procedure to synthesize palladium-silver alloys supported on high-surface-area α-Al 2 O 3 (HSA-α-Al 2 O 3 ) as catalysts for the selective hydrogenation of such acetylene streams. The mechanochemical (dry) synthesis of catalytic materials presents a higher atom efficiency and lower environmental impact compared to wet methods. Furthermore, the high-energy conditions provided by the mechanochemical treatment can provide materials with improved properties compared to the materials obtained by traditional methods, e.g., materials with higher surface area. Thus, mechanochemistry is promising for obtaining new, high-performant catalysts. The synthesized palladium-silver materials display high selectivity towards ethylene with significantly higher stability with t OS under the harsh reaction conditions compared to materials synthesized by wet impregnation. However, systematic approaches to navigate the immense space of possible materials that can be made mechanochemically are not yet available. Here, we combine the advantages of the mechanochemical synthesis with focused AI in order to efficiently design improved palladium-based bimetallic and trimetallic systems for the selective hydrogenation of concentrated acetylene streams.