Second brain, forgotten organ, individual’s identity card, and host’s fingerprint are the few collective terms that are often used to describe the gut microbiome because of its variability, accountability, and its role in deciding the host’s health. Also, the understanding of this host health–gut microbiota relationship can create an opportunity to control an individual’s health by manipulating the gut microbiota composition. Several approaches like administration of probiotic, prebiotics, synbiotics, faecal microbiota transplantation have been tried to mitigate the dysbiosis originated ill effects. But the effects of these approaches are highly generic and non-specific. This creates the necessity to design personalized medicine that focuses on treatment of specific disease considering the individual specific gut microbiome. The health promoting commensals could be the new promising prophylactic and therapeutic agents for designing personalized medicine. These commensals are designated as next-generation probiotics (NGPs) and their unusual characteristics, unknown identity and special growth requirements have presented difficulties for researcher, industrial exploitation, and regulatory agencies. In this perspective, this review discusses the concept of NGPs, NGP candidates as tool for designing personalized medicine, designer probiotics as NGPs, required regulatory framework, and propose a road map to develop the NGP based product.