Neonatal necrotizing enterocolitis (NEC) is a multifactorial disease of unspecified etiology. The lack of data on etiological factors and the complexity of pathogenetic mechanisms determine the complexity of NEC modeling. The authors involved in the study of the pathogenesis of NEC and the development of current treatments seek to model in the experiment the conditions that occur in clinical practice. Thus, this study aimed to analyze the options for the experimental modeling of neonatal NECs described in the public domain. Thus, more than 50 relevant scientific publications in databases such as Google Scholar, PubMed, Scopus (publishers Elsevier), and eLibrary (from 2000 to 2022) were reviewed. This paper describes the most current methods of modeling NEC, including in vitro (using cells and cell cultures), in vivo (in laboratory animals such as mice, rats, rabbits, and pigs), and ex vivo (using cadaver material) experiments.