Necrotizing enterocolitis is a multifactorial disease with complex pathogenesis, predominantly affecting preterm babies and representing neonatal urgency, still with high mortality and long-term morbidity, considering gastrointestinal complications, somatic growth retardation, and secondary lung and brain lesions. Although complex pathogenesis exists, three main risk factors are: intestinal immunological immaturity, intestinal colonization with pathogenic bacteria (dysbiosis), and enteral formula feeding. Clinical and scientific knowledge explain complex pathogenesis and create a basis for the implementation of novel nutritional and pharmacological measures for the purpose of disease prevention. The aim of this work is epidemiological, clinical, immunological, and microbiological knowledge integration for the implementation of novel preventive and therapeutic strategies. Necrotizing enterocolitis in term newborns with different pathogenesis and clinical presentation is not the subject of this text.