INTRODUCTION AND OBJECTIVES: Metabolic dysfunction-associated steatotic liver disease (MASLD), formerly non-alcoholic fatty liver disease, is a growing global health challenge. This study examines the global burden of MASLD from 1990 to 2021 and projects data for 2045. MATERIALS AND METHODS: Using data from the Global Burden of Disease (GBD) Study 2021, the study analyzed MASLD across 204 countries from 1990 to 2021, focusing on prevalence, incidence, deaths, and disability-adjusted life years (DALYs). Linear and Joinpoint regression assessed trends, an age-period-cohort model evaluated health outcomes, and a Bayesian model forecasted future cases. RESULTS: In 2021, approximately 1.27 billion people globally had MASLD, with a higher prevalence in males (51.41 %). There were 48.35 million new cases, primarily in males (52.24 %). The age-standardized prevalence rate (ASPR) increased from 12,085.09 in 1990 to 15,018.07 per 100,000 in 2021 (AAPC 0.71). The age-standardized incidence rate (ASIR) rose from 475.54 to 593.28 per 100,000 (AAPC 0.71). MASLD caused 138,328 deaths, with females experiencing higher mortality (52.18 %). East Asia, South Asia, and North Africa/Middle East had the highest prevalence and incidence rates, while Western Europe showed the fastest growth. By 2045, ASIR is projected to reach 928.10 per 100,000, resulting in 667.58 million new cases, predominantly affecting males. CONCLUSIONS: MASLD poses a significant burden with notable gender and regional disparities. The projected increase by 2045 underscores the need for urgent public health interventions and targeted strategies to mitigate this growing epidemic.