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Despite the number of HTx performed annually in worldwide continues to increase, complications of HTx still impact the quality of life and long-term prognosis, including rejection, infection, and allograft dysfunction. Endomyocardial biopsy remains the gold standard for monitoring cardiac allograft rejection post-heart transplantation, yet its invasiveness and interobserver error in histologic grading necessitate the development of novel noninvasive biomarkers to elucidate rejection mechanisms and progression. Cardiac allograft vasculopathy, a critical determinant of long-term outcomes, is challenging to detect early via intravascular ultrasound, underscoring the potential of plasma biomarkers for disease surveillance. Omic technologies usually refers to the application of multiple high-throughput screening technologies enabling comprehensive analysis of biological systems at a molecular level. Multi-omics technologies, including genomics(donor-derived cell-free DNA), transcriptomics(microRNAs panels, gene expression profiling), proteomics(cell signaling molecule), and metabolomics(ex situ heart perfusion), have demonstrated significant promise in post-transplant monitoring. These approaches provide personalized risk stratification and mechanical insights into cardiac allograft rejection, primary graft dysfunction, and cardiac allograft vasculopathy. Single\u2013cell omics technologies and machine learning algorithms further resolve cellular heterogeneity and improve predictive modeling, thereby enhancing the clinical translatability of multi-omics data. This comprehensive review synthesizes these advances and highlights the transformative potential of integrating multi-omics with advanced analytics to achieve precision monitoring and therapy in HTx, ultimately improving long-term patient outcomes.<\/jats:p>","DOI":"10.1186\/s12967-025-06772-0","type":"journal-article","created":{"date-parts":[[2025,7,1]],"date-time":"2025-07-01T05:15:00Z","timestamp":1751346900000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Transforming heart transplantation care with multi-omics insights"],"prefix":"10.1186","volume":"23","author":[{"given":"Zhengbang","family":"Zou","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianing","family":"Han","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiyuan","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shanshan","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinhe","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8929-7178","authenticated-orcid":false,"given":"Sheng","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,7,1]]},"reference":[{"issue":"10","key":"6772_CR1","doi-asserted-by":"publisher","first-page":"1035","DOI":"10.1016\/j.healun.2021.07.015","volume":"40","author":"KK Khush","year":"2021","unstructured":"Khush KK, Hsich E, Potena L, Cherikh WS, Chambers DC, Harhay MO, et al. 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