Current developments in microbial research and synthetic biology have motivated the investigators to develop a diverse range of engineered microbes expressing valuable biotherapeutics targeting a range of human clinical applications. Probiotics, developed through a recombinant approach, represent the new era of whole cell-mediated biotherapeutics. These engineered probiotics are target specific and have high endurance capability, which makes them a perfect vaccine or drug carrying vehicle in the host system. This chapter outlines the diverse capabilities of biotherapeutics expressed through engineered microbes as a potent engineered probiotic, for the treatment of different chronic human pathologies including metabolic disorder, malignancy, chronic inflammation bowel disease concerned with the gastrointestinal tract and autoimmune disorders, respectively. This chapter also entails the significant advancement in the area of reprogrammed microbes used as an effective bio-scavenger, for the remediation of toxic heavy metals from the environment. The sustainable production of target specific biotherapeutics from a recombinant microbiome will enable us to overcome the burden of expensive drugs with severe side effects. This modern concept of engineered biotherapeutics will narrow down many technical and economic barriers associated with drug development globally. The modern era on microbial biotherapeutics will ensure healthy lives and promote the well-being of the global population.