Despite the critical role of microbiota-derived molecules, the structural characterization and functional understanding of such molecules remain limited. A significant portion of metabolites undergo changes, irrespective if they are aquatic, soil, plant, animal, and human microbiome ecosystems, when the microbiome is altered. Typically, only about 10% of the data can be attributed to a molecular structure, with merely 1-2% traceable to microbial origins. However, sequencing indicates that microbiomes often possess 100-150 times the metabolic capacity compared to host ecosystems. Understanding the microbiome mechanistically and gaining control over microbiomes necessitate novel tools to discover all microbiota-derived metabolites and elucidate their functional roles. Humans, along with other ecosystems, are comprised of microbial-derived metabolites via three primary sources: 1) microbial metabolism of host-derived metabolites; 2) microbial digestion of molecules from food and beverages; and 3) microbial synthesis of metabolites using proteins encoded by genetic elements, often organized as gene clusters across bacteria, archaea, fungi, and recently discovered to be widespread in phages. Furthermore, microbial metabolites can stem from the microbial processing of xenobiotics beyond food, including plasticizers, pollutants, medications, and potentially environmental molecules absorbed through the skin or inhalation. This conference aims to explore the latest technological advancements for discovering new microbiome-derived metabolites, identifying the genes responsible for their production, and understanding of their functional roles. These insights hold promise for various applications in managing health and disease in agriculture, environment and medicine.