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Congenital TEF arises from embryological malformations, often coexisting with esophageal atresia (EA), while acquired TEF primarily stems from malignancies, radiotherapy, or trauma. This condition disrupts normal anatomical functions, leading to significant clinical issues, such as aspiration, respiratory infections, and malnutrition. The current review consolidates findings on the etiology, classification, and pathological mechanisms of TEF, emphasizing how genetic, developmental, and external factors shape its occurrence and progression. Diagnostic advancements, including radiological imaging, endoscopic evaluations, and newer monitoring techniques, have refined clinical assessment. Treatment paradigms for TEF vary from minimally invasive endoscopic interventions, to traditional open and innovative surgical approaches. Conservative management, such as nutritional and anti\u2010infective therapies, remains vital, especially for milder cases. Emerging therapies in regenerative medicine\u2014such as tissue\u2010engineered scaffolds and platelet\u2010rich plasmaoffer transformative potential for refractory cases. Future advancements are oriented toward exploring 3D printing, artificial intelligence, and precision medicine. The necessity of multidisciplinary collaboration is underscored in optimizing holistic patient care. While significant progress has improved cure rates and long\u2010term outcomes, continued research on innovative technologies and clinical trials addressing knowledge gaps in long\u2010term efficacy remains crucial.<\/jats:p>","DOI":"10.1002\/advs.202502825","type":"journal-article","created":{"date-parts":[[2025,9,2]],"date-time":"2025-09-02T14:29:41Z","timestamp":1756823381000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Comprehensive Insights into Tracheoesophageal Fistula Pathophysiology, Diagnosis, Treatment, and Future Directions"],"prefix":"10.1002","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-8529-0896","authenticated-orcid":false,"given":"Gang","family":"Li","sequence":"first","affiliation":[{"name":"Pediatric Emergency and PICU Northwest Women and Children's Hospital  No.1616 Yanxiang Road, Yanta District Xi'an City 710061 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