Inflammatory bowel disease (IBD) is an auto-immune condition characterized by chronic gastrointestinal inflammation. The incidence of pediatric IBD, particularly the early onset disease subtypes, has been increasing internationally. In contrast to later-onset IBD, recent literature indicates that early-onset (between 3 -5 years) and very early-onset (between 0 -2 years) patients present with a more severe and aggressive disease. A comprehensive review of the literature indicates that the gut microbiome, which is heavily influenced in the early life, is reduced in IBD patients and hence plays a role in regulating gastrointestinal homeostasis. While many genes have been confirmed to be associated with IBD, only a portion of those genes have been shown to cause pediatric IBD.The IL-10/STAT3 pathway is a well-studied gene pathway as is, involved in maintaining immune homeostasis in both acute and chronic inflammation. Accumulating evidence indicates that IL-10/STAT3 pathway is a key player in pediatric IBD. New mutations identified within the IL-10 pathway have been shown to disrupt immune homeostasis and cause gastrointestinal inflammation. Furthermore, significant epistatic interactions have been demonstrated between different single-nucleotide polymorphisms of IL-10 genes suggesting that understanding gene interactions within the IL-10//STAT3 pathway may be key to understanding more about IBD pathogenesis. Heme oxygenase 1 (HO-1) is speculated to be regulated by the IL-10/STAT3 pathway and hence involved in pediatric IBD formation. This review aims to provide an overview of pediatric IBD and discuss the role of the gut microbiome, IL-10/STAT3 pathway, and HO-1 gene in modulating immune homeostasis in IBD pathogenesis.