Necrotizing enterocolitis (NEC) remains one of the most severe diseases of the neonatal period and is associated with high mortality and a significant risk of serious complications in preterm infants. The aim of this study was to analyze current evidence regarding predictors of NEC development, evaluate their prognostic significance, and assess the possibilities for early diagnosis. Clinical, perinatal, laboratory, and instrumental markers are discussed, along with the prospects for integrating multifactorial prediction models. Particular attention is paid to biomarkers of intestinal injury, alterations in gut microbiota, and emerging technologies aimed at improving the early identification of high-risk neonates. The development of comprehensive predictive approaches may contribute to personalized management and improved outcomes in newborns with necrotizing enterocolitis.