ABSTRACT Microbe therapeutics (MTs) are an emerging class of FDA-regulated drugs that include microbiota transplants, spore-based therapeutics, living microbes (e.g. probiotics), and genetically engineered bacteria that secrete therapeutics. MTs are currently being investigated in a wide-range of clinical trials to treat inflammation, pathogenic infections, and genetic disorders. MTs are being used in the gastrointestinal (GI) tract, on the skin, and on mucosal barriers (e.g. oral cavity). The mechanism of action that governs MT efficacy can range from microbiome modulation, to biological barrier reinforcement, to metabolite or biologic secretion. These mechanisms are fundamentally distinct and each one is tied to a different MT. As such, we hypothesize that each MT has distinct delivery requirements based on their mechanism of action, the target site/organ, and the specific properties of each individual MT. To this end, a key and unaddressed challenge is identifying the ideal delivery parameters for MTs so that approaches to improve MT delivery can be developed and employed. To date, all clinically evaluated MTs are delivered via technologies that were originally designed and optimized for small molecules and recent failures in MT clinical trials have been attributed to dosing inconsistencies. For other drugs, dosing has been addressed and improved through the adoption of formulation approaches from the pharmaceutical sciences and drug delivery approaches from engineering. My goals over the next five years are to: (i) understand the key requirements for successful MT delivery, (ii) introduce pharmaceutical sciences and engineering-based drug delivery approaches to formulate and subsequently improve the delivery of MTs, and (iii) highlight the utility of MT delivery systems in enabling MT treatment of diseases/disorders that affect distinct tissues, such as infections on the skin or infection in the gastrointestinal tract. My program will focus on defining and subsequently addressing the MT-specific formulation and delivery challenges. We will address gaps in knowledge that have limited the rational development of MT-specific delivery systems related to basic questions such as how important is delivery of MTs to the right place, at the right time, and at the right dose. My program will be the first to attempt a systematic approach to asking and answering these key questions towards improved formulation and delivery of MTs.