Accumulating evidence underscores the pivotal involvement of the interleukin-33 (IL-33)/suppression of tumorigenicity 2 (ST2) signaling pathway in critical aspects of MASLD pathophysiology, such as metabolic balance, oxidative stress response, intestinal barrier integrity, microbiota dynamics, inflammatory processes, hepatic fibrosis, and tumor development. This evidence concerns the gene IL33 and metabolic dysfunction-associated steatotic liver disease.