Retinopathy of Prematurity (ROP) is a proliferative vascular disease affecting the retina of preterm infants, a major cause of childhood blindness worldwide. It is characterized by abnormal retinal vascularization and can progress to retinal detachment and severe visual impairment if untreated. ROP incidence varies geographically, influenced by neonatal care quality and preterm birth rates. Despite advancements in ROP research and treatment, its incidence continues to rise, leading to increased healthcare costs. Screening and early intervention are crucial for preventing ROP-related blindness, with cost-effectiveness analyses highlighting the importance of screening tools. The pathophysiology of ROP involves complex molecular mechanisms, including hypoxia and redox signaling pathways. Hypoxia-inducible factor 1α (HIF-1α) and vascular endothelial growth factor (VEGF) play key roles in retinal angiogenesis. Hyperoxia in preterm infants suppresses HIF-1α and VEGF, leading to oxidative stress and avascular retinal regions. Inflammatory factors, such as cytokines and reactive oxygen species (ROS), contribute to retinal cell death and choroidal degeneration. Nitro-oxidative stress, driven by enzymes like NADPH oxidase (NOX), exacerbates vaso-obliteration and neoangiogenesis. Recent studies have explored molecular targets for ROP treatment, including antioxidant strategies, modulation of the Nrf2 pathway, and targeting the STAT3 signaling pathway. Anti-VEGF therapies, such as bevacizumab and ranibizumab, have shown promise in reducing ROP progression. Emerging treatments include targeting HIF-1α and VEGF, as well as exploring the role of steroids and other molecules like stanniocalcin-1. Caffeine and vitamin A have also been investigated for their potential in preventing ROP. These advancements highlight the need for innovative therapeutic strategies to improve ROP management and reduce visual impairment in preterm infants.Retinopathy of Prematurity (ROP) is a proliferative vascular disease affecting the retina of preterm infants, a major cause of childhood blindness worldwide. It is characterized by abnormal retinal vascularization and can progress to retinal detachment and severe visual impairment if untreated. ROP incidence varies geographically, influenced by neonatal care quality and preterm birth rates. Despite advancements in ROP research and treatment, its incidence continues to rise, leading to increased healthcare costs. Screening and early intervention are crucial for preventing ROP-related blindness, with cost-effectiveness analyses highlighting the importance of screening tools. The pathophysiology of ROP involves complex molecular mechanisms, including hypoxia and redox signaling pathways. Hypoxia-inducible factor 1α (HIF-1α) and vascular endothelial growth factor (VEGF) play key roles in retinal angiogenesis. Hyperoxia in preterm infants suppresses HIF-1α and VEGF, leading to oxidative stress and avascular retinal regions. Inflammatory factors, such as cytokines and reactive oxygen species (ROS), contribute to retinal cell death and choroidal degeneration. Nitro-oxidative stress, driven by enzymes like NADPH oxidase (NOX), exacerbates vaso-obliteration and neoangiogenesis. Recent studies have explored molecular targets for ROP treatment, including antioxidant strategies, modulation of the Nrf2 pathway, and targeting the STAT3 signaling pathway. Anti-VEGF therapies, such as bevacizumab and ranibizumab, have shown promise in reducing ROP progression. Emerging treatments include targeting HIF-1α and VEGF, as well as exploring the role of steroids and other molecules like stanniocalcin-1. Caffeine and vitamin A have also been investigated for their potential in preventing ROP. These advancements highlight the need for innovative therapeutic strategies to improve ROP management and reduce visual impairment in preterm infants.