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By sequencing all nucleic acids in a sample, mNGS overcomes the narrow detection scope and slow turnaround of conventional tests, substantially improving pathogen detection. In conditions such as meningitis\/encephalitis, sepsis, and pneumonia, mNGS frequently identifies etiologies missed by routine diagnostic tests, thereby facilitating earlier pathogen\u2010directed therapy and, in selected settings, improving clinical management and outcomes. This approach is particularly valuable for immunocompromised, pediatric, and intensive care unit (ICU) patients with atypical infections. Currently, clinical mNGS workflows primarily rely on short\u2010read sequencing platforms (e.g., Illumina), whereas long\u2010read platforms (e.g., Nanopore, PacBio) offer advantages for rapid or high\u2010resolution applications. Optimized bioinformatics and stringent quality control are essential for reliable results. Beyond clinical diagnostics, mNGS provides valuable genetic data on antimicrobial resistance (AMR) and pathogen phylogeny, supporting public health and outbreak surveillance (e.g., wastewater monitoring and variant tracking). Current challenges include distinguishing colonization from infection, interpreting sequencing data quantitatively, and reducing cost and turnaround time. Looking ahead, emerging strategies such as targeted panels, rapid automated workflows, and host\u2011response integration are expected to further shorten time\u2011to\u2011result and improve diagnostic specificity. Parallel progress in ethical and regulatory frameworks remains essential to ensure responsible implementation. To support clinical adoption, a standardized framework for clinical interpretation of mNGS results, together with associated training, has been developed and implemented. Overall, mNGS is likely to become an increasingly important component of infectious disease diagnostics, with ongoing innovations expected to broaden its clinical and epidemiological impact.<\/jats:p>","DOI":"10.1002\/mlf2.70078","type":"journal-article","created":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T14:55:38Z","timestamp":1777560938000},"page":"148-163","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Emerging role of metagenomic next\u2010generation sequencing in infectious disease diagnostics: Clinical integration and future directions"],"prefix":"10.1002","volume":"5","author":[{"given":"Tingting","family":"Fang","sequence":"first","affiliation":[{"name":"Department of Infectious Diseases, Zhongshan Hospital Fudan University Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feifei","family":"Yuan","sequence":"additional","affiliation":[{"name":"Department of 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