This study provides a comprehensive review of the progression and mechanisms of chronic radiation-induced skin injury, focusing on fibrosis. The authors discuss the initial radiation exposure and its acute and chronic effects, highlighting the transition from acute to chronic radiation skin injury. They detail the molecular mechanisms involved, including the activation of fibroblasts into myofibroblasts, the role of TGF-β in fibrosis, and the involvement of the immune system. The review also explores the impact of epigenetic regulators, extracellular matrix (ECM) proteins, and the fibrotic microenvironment. Additionally, the authors discuss potential therapeutic strategies, such as targeting TGF-β, using biomaterials and tissue engineering, and integrating computational biology and bioinformatics. The study emphasizes the need for targeted therapies to improve patient quality of life and manage radiation-induced skin fibrosis effectively.This study provides a comprehensive review of the progression and mechanisms of chronic radiation-induced skin injury, focusing on fibrosis. The authors discuss the initial radiation exposure and its acute and chronic effects, highlighting the transition from acute to chronic radiation skin injury. They detail the molecular mechanisms involved, including the activation of fibroblasts into myofibroblasts, the role of TGF-β in fibrosis, and the involvement of the immune system. The review also explores the impact of epigenetic regulators, extracellular matrix (ECM) proteins, and the fibrotic microenvironment. Additionally, the authors discuss potential therapeutic strategies, such as targeting TGF-β, using biomaterials and tissue engineering, and integrating computational biology and bioinformatics. The study emphasizes the need for targeted therapies to improve patient quality of life and manage radiation-induced skin fibrosis effectively.