<p>Next-generation probiotics (NGPs) represent a promising advancement in microbial therapeutics, offering targeted and personalized interventions for various health disorders. Unlike traditional probiotics, NGPs focus on specific bacterial strains with enhanced functional properties, achieved through genetic engineering and next-generation sequencing technologies. Their applications span gastrointestinal disorders, metabolic syndromes, immune-related conditions, skin diseases, oral health, and animal well-being. NGPs contribute to gut microbiome modulation, metabolic regulation, and immune system enhancement, demonstrating therapeutic potential in clinical studies. Regulatory challenges persist, as NGPs fall under different legal classifications worldwide, necessitating rigorous safety assessments, including whole-genome sequencing to evaluate virulence and antibiotic resistance. Clinical trials continue to validate their efficacy in diverse conditions, emphasizing the need for standardized guidelines. Furthermore, novel probiotic delivery systems, including microdevices and targeted coatings, are being explored to improve bacterial viability and colonization in the gut. Identifying new probiotic strains with enhanced survival capabilities and elucidating their mechanisms of action remain critical for advancing probiotic science. Cost-effectiveness and commercialization of NGPs present opportunities for broader healthcare integration, with increasing research supporting their role in disease prevention and treatment. This review highlights the multifaceted potential of NGPs and the challenges that must be addressed for their successful implementation in modern healthcare.</p>