Chronic liver disease affects more than 1.5 billion people and most commonly results from chronic infection with hepatitis B virus (HBV), hepatitis C virus (HCV), or steatotic liver diseases. Effective treatments exist for viral infections but effective approaches to alter the course of MASLD are still understudied. The most common steatotic liver disease is Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) has become a major public health problem because of its high world-wide prevalence of ~30%, association with serious cardiometabolic abnormalities, including diabetes, the metabolic syndrome and coronary heart disease, and potential progression to severe liver disease, including advanced fibrosis/cirrhosis and hepatocellular carcinoma. The goals of this Keystone Conference are to provide the latest data that: 1) provide new insights into the molecular and physiological mechanisms that cause hepatic steatosis and its progression to advanced fibrosis; 2) identify the key metabolic targets for effective therapeutic intervention; 2) define and clarify the clinical implications of the underappreciated association between sarcopenia and MASLD and its therapeutic options; 3) critically evaluate the role of weight loss and exercise in treating people with MASLD and the most effective intervention strategies to prevent disease progression and improve co-morbidities; and 4) provide the rationale and results of the most promising early stage pharmacological interventions for MASLD. The expert speakers represent basic and translational researchers, and scientists from industry whose collective expertise will provide a comprehensive overview of how and why metabolic dysfunction causes MASLD and what interventions provide the best therapeutic opportunities for this increasingly common disease.