BACKGROUND & AIMS: Although the clinical burden of metabolic dysfunction-associated steatohepatitis (MASH) is well-known, its economic burden is less well-described. We estimated MASH's economic burden in several regions of the world including the United States (U.S.), Germany, Spain, France, Italy, the United Kingdom (UK), Japan, Saudi Arabia, and Brazil over the next 2 decades. METHODS: A 1-year cycle Markov model projected MASH progression from 2021 to 2040, incorporating 2020 prevalent cases and annual incident cases (2021-2040). Transition probabilities were derived from the literature, calibrated using national estimates of prevalence rates for type 2 diabetes and obesity, and adjusted against observed incidences of decompensated cirrhosis, hepatocellular carcinoma, and liver transplants. MASH-related direct costs, productivity losses, and quality-of-life were updated annually based on projected disease stage. Future economic burdens were adjusted using country-specific inflation rates from the International Monetary Fund. RESULTS: MASH prevalence is projected to increase (2021-2040): United States (6.71%-7.41%), Germany (4.43%-4.97%), Spain (4.50%-5.38%), France (4.04%-4.50%), Italy (4.58%-5.37%), United Kingdom (4.75%-5.21%), Japan (3.67%-5.02%), Brazil (7.19%-7.52%), and Saudi Arabia (7.39%-7.50%). The prevalence of advanced MASH (F3- compensated cirrhosis, decompensated cirrhosis, hepatocellular carcinoma, and liver transplantations) is expected to increase by ≥20% in all countries. Direct annual medical costs are projected to more than double, increasing from $34.97 to $78.59 billion in the United States, $0.83 to $1.82 billion in Germany, $1.48 to $3.50 billion in Spain, $1.28 to $2.90 billion in France, $1.34 to $3.00 billion in Italy, $2.18 to $5.29 billion in the United Kingdom, $1.20 to $2.33 billion in Japan, $3.41 to $9.81 billion in Brazil, and $1.72 to $3.96 billion in Saudi Arabia. Work productivity losses are projected to more than double in most countries, and health-related quality of life will decline modestly as the burden of advanced disease increases CONCLUSIONS: Without intervention, the clinical, economic, and quality-of-life burden of MASH is projected to increase across most regions of the world. These findings highlight the urgent need for both national and global strategies to reduce the negative impact of MASH on individuals and society.