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This mini-review argues that AI-driven multi-omics biomarkers offer a valuable shift toward systems-level, model-derived probabilities integrating genomic, transcriptomic, proteomic, metabolomic, and imaging information to explain and predict disease behavior more faithfully. We synthesize recent advances across three domains: (i) computational strategies for multi-omics integration, from classical penalized regression and ensemble learning to deep multimodal architectures and foundation-model embeddings; (ii) therapeutically relevant biomarker classes across tissue, liquid biopsy, and imaging modalities; and (iii) emerging pathways for embedding these biomarkers into clinical decision support. We highlight validation, interpretability, and robust handling of missing modalities as prerequisites for clinical trust, and outline how biomarker-driven trials, standardized reporting (e.g., TRIPOD + AI), and privacy-preserving data consortia can move AI-driven multi-omics biomarkers toward clinical and regulatory maturity.<\/jats:p>","DOI":"10.3389\/fphar.2026.1953714","type":"journal-article","created":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T08:52:43Z","timestamp":1790671963000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["AI-driven multi-omics biomarkers in precision breast cancer therapeutics: from discovery to clinical translation"],"prefix":"10.3389","volume":"17","author":[{"given":"Dimitrios","family":"Stylianakis","sequence":"first","affiliation":[{"name":"University Hospital","place":["Heraklion, Greece"]},{"name":"School of Medicine, University of Crete","place":["Heraklion, Greece"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rodrigo","family":"S\u00e1nchez-Bayona","sequence":"additional","affiliation":[{"name":"Medical Oncology Department, Hospital Universitario 12 de Octubre","place":["Madrid, Spain"]},{"name":"Medical Oncology Department, Hospital Universitario 12 de Octubre, Instituto de Investigaci\u00f3n Sanitaria Hospital 12 de Octubre (imas12)","place":["Madrid, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nerina","family":"Denaro","sequence":"additional","affiliation":[{"name":"Medical Oncology Unit, Fondazione IRCCS Ca\u2019 Granda, Ospedale Maggiore Policlinico","place":["Milan, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cinzia","family":"Solinas","sequence":"additional","affiliation":[{"name":"Medical Oncology Unit, University Hospital of Cagliari","place":["Cagliari, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,29]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"500002","DOI":"10.1016\/j.remnie.2024.500002","article-title":"Intra and peritumoral PET radiomics analysis to predict the pathological response in breast cancer patients receiving neoadjuvant chemotherapy","volume":"43","author":"Aksu","year":"2024","journal-title":"Rev. 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