Nonalcoholic fatty liver disease (NAFLD), also known as metabolic dysfunction-associated steatotic liver disease (MASLD), has a complex pathogenesis with increasing incidence and prevalence; however, the treatment options remain limited. The mitochondria-associated endoplasmic reticulum membrane (MAM) coordinates calcium signaling, lipid synthesis, and endoplasmic reticulum stress responses via dynamic contact interfaces, and its functional aberration is closely related to MASLD. Emerging evidence indicates that MASLD progression is strongly associated with ferroptosis driven by iron-dependent lipid peroxidation, and MAM plays a regulatory role in the ferroptosis process by modulating key pathways involving lipid peroxidation and iron metabolism. This review elucidates the intricate structural composition and ferroptosis regulatory mechanism of MAM and discusses the challenges and future prospects of MAM-targeted therapies for MASLD, aiming to provide novel perspectives for the treatment of MASLD.