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Multi\u2010omics\u2010driven precision medicine (MODPM) addresses this lack by integrating genomics, epigenomics, transcriptomics, proteomics, metabolomics, microbiome, and clinical context into a multiscale framework that links molecular mechanisms, tissue organization, and patient trajectories. In this review, we propose a conceptual framework for MODPM and examine how advances in multi\u2010omics technologies, artificial intelligence (AI), and foundation models are reshaping disease modeling, drug development, and precision intervention. We summarize the biological contributions of major omics layers and discuss how AI supports cross\u2010modal representation learning, contextual modeling, and perturbation\u2010aware prediction. We highlight drug development as a key translational application of MODPM and further discuss its clinical relevance across three major disease contexts: cancer, autoimmune diseases, and metabolic disorders, including cardiometabolic and renal\u2013metabolic diseases. These examples illustrate how MODPM can support target discovery, disease endotyping, treatment response prediction, and clinical monitoring by analyzing shared mechanisms such as immune dysregulation, metabolic remodeling, chronic inflammation, tissue microenvironmental changes, and gene\u2013environment interactions. Across these settings, MODPM enables finer molecular stratification, the identification of pathway\u2010dominant disease states, improved response prediction, and dynamic treatment monitoring. We also discuss key barriers to implementation, including data heterogeneity, limited cohort diversity, polygenic complexity, workflow constraints, cost, and ethical issues related to privacy, consent, and data ownership. Overall, the value of MODPM lies not in stacking additional data layers but in building a multiscale, continuously learnable framework to link biological heterogeneity to clinically interpretable and actionable decisions.<\/jats:p>","DOI":"10.1002\/imt2.70165","type":"journal-article","created":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T06:59:32Z","timestamp":1787727572000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Multi\u2010omics\u2013driven precision medicine"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6807-8099","authenticated-orcid":false,"given":"Huibo","family":"Li","sequence":"first","affiliation":[{"name":"School of Pharmacy, Faculty of Medicine, Laboratory of Drug Discovery from Natural Resources and Industrialization, Macau University of Science and Technology Macau SAR China"},{"name":"Department of Pharmacy Peking University Third Hospital; Peking University Therapeutic Drug Monitoring and Clinical Toxicology Center; Institute for Drug Evaluation, Peking University Health Science Center Beijing China"},{"name":"State Key Laboratory of Natural and Biomimetic Drugs, Peking University Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhe","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Peking University Third Hospital; Peking University Therapeutic Drug Monitoring and Clinical Toxicology Center; Institute for Drug Evaluation, Peking University Health Science Center Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yifan","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Faculty of Medicine, Laboratory of Drug Discovery from Natural Resources and Industrialization, Macau University of Science and Technology Macau SAR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yao","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of General Surgery Cancer Center, Peking University Third Hospital Beijing China"},{"name":"Beijing Key Laboratory for Interdisciplinary Research in Gastrointestinal Oncology, Peking University Third Hospital Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gaofei","family":"Hu","sequence":"additional","affiliation":[{"name":"The Institute of Cardiovascular Sciences and Institute of Systems Biomedicine, School of Basic Medical Sciences, State Key Laboratory of Vascular Homeostasis and Remodeling, NHC Key Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides, Beijing Key Laboratory of Cardiovascular Receptors Research, Health Science Center, Peking University Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Zeng","sequence":"additional","affiliation":[{"name":"Department of Immunology School of Basic Medical Sciences, NHC Key Laboratory of Medical Immunology, Medicine Innovation Center for Fundamental Researches on Major Immunology\u2010Related Diseases, Peking University Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhanqun","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Peking University Third Hospital; Peking University Therapeutic Drug Monitoring and Clinical Toxicology Center; Institute for Drug Evaluation, Peking University Health Science Center Beijing China"},{"name":"Department of General Surgery Cancer Center, Peking University Third Hospital Beijing China"},{"name":"Beijing Key Laboratory for Interdisciplinary Research in Gastrointestinal Oncology, Peking University Third Hospital Beijing China"},{"name":"Institute of Advanced Clinical Medicine, Peking University Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zixuan","family":"Zhao","sequence":"additional","affiliation":[{"name":"Ministry of Education Key Laboratory of Bioinformatics, Bioinformatics Division at the Beijing National Research Center for Information Science and Technology, Center for Synthetic and Systems Biology, Department of Automation Tsinghua University Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of General Surgery Cancer Center, Peking University Third Hospital Beijing China"},{"name":"Beijing Key Laboratory for Interdisciplinary Research in Gastrointestinal Oncology, Peking University Third Hospital Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Hu","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Faculty of Medicine, Laboratory of Drug Discovery from Natural Resources and Industrialization, Macau University of Science and Technology Macau SAR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuxuan","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Peking University Third Hospital; Peking University Therapeutic Drug Monitoring and Clinical Toxicology Center; Institute for Drug Evaluation, Peking University Health Science Center Beijing China"},{"name":"Department of Pharmacy Children's Hospital, Tianjin University Tianjin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meng","family":"Su","sequence":"additional","affiliation":[{"name":"College of Pharmacy, University of Louisiana at Monroe Monroe Louisiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology Peking University Third Hospital Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew","family":"Whiteman","sequence":"additional","affiliation":[{"name":"University of Exeter Medical School Exeter UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Fu","sequence":"additional","affiliation":[{"name":"Department of General Surgery Cancer Center, Peking University Third Hospital Beijing China"},{"name":"Beijing Key Laboratory for Interdisciplinary Research in Gastrointestinal Oncology, Peking University Third Hospital Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chao","family":"Zhong","sequence":"additional","affiliation":[{"name":"Department of Immunology School of Basic Medical Sciences, NHC Key Laboratory of Medical Immunology, Medicine Innovation Center for Fundamental Researches on Major Immunology\u2010Related Diseases, Peking University Beijing China"},{"name":"Department of Rheumatology and Immunology Peking University Third Hospital Beijing China"},{"name":"Department of Gastroenterology Peking University First Hospital Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4473-6936","authenticated-orcid":false,"given":"Lemin","family":"Zheng","sequence":"additional","affiliation":[{"name":"The Institute of Cardiovascular Sciences and Institute of Systems Biomedicine, School of Basic Medical Sciences, State Key Laboratory of Vascular Homeostasis and Remodeling, NHC Key Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides, Beijing Key Laboratory of Cardiovascular Receptors Research, Health Science Center, Peking University Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Long","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Peking University Third Hospital; 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