Metabolic dysfunction-associated steatotic liver disease (MASLD), previously known as nonalcoholic fatty liver disease (NAFLD), encompasses a range of liver conditions from steatosis to nonalcoholic steatohepatitis (NASH). The prevalence of MASLD, especially among patients with metabolic syndrome, highlights its growing global impact. The pathogenesis of MASLD involves metabolic dysregulation, inflammation, oxidative stress, genetic factors, and mitochondrial dysfunction. Recent studies have emphasized the critical role of mitochondrial dysfunction in the progression of MASLD. Therapeutically, enhancing mitochondrial function has gained significant interest, along with lifestyle changes and pharmacological interventions targeting mitochondrial processes. The FDA's approval of resmetir for metabolic-associated steatohepatitis (MASH) with fibrosis marks a significant step forward. However, further research is essential to fully understand MASLD-related mitochondrial dysfunction. Innovative strategies such as gene editing and small-molecule modulators, alongside lifestyle interventions, can potentially improve MASLD treatment. Drug repurposing and new targets will advance MASLD therapy, addressing its increasing global burden. This review aims to provide a better understanding of the role of mitochondrial dysfunction in MASLD and identify more effective preventive and treatment strategies.Metabolic dysfunction-associated steatotic liver disease (MASLD), previously known as nonalcoholic fatty liver disease (NAFLD), encompasses a range of liver conditions from steatosis to nonalcoholic steatohepatitis (NASH). The prevalence of MASLD, especially among patients with metabolic syndrome, highlights its growing global impact. The pathogenesis of MASLD involves metabolic dysregulation, inflammation, oxidative stress, genetic factors, and mitochondrial dysfunction. Recent studies have emphasized the critical role of mitochondrial dysfunction in the progression of MASLD. Therapeutically, enhancing mitochondrial function has gained significant interest, along with lifestyle changes and pharmacological interventions targeting mitochondrial processes. The FDA's approval of resmetir for metabolic-associated steatohepatitis (MASH) with fibrosis marks a significant step forward. However, further research is essential to fully understand MASLD-related mitochondrial dysfunction. Innovative strategies such as gene editing and small-molecule modulators, alongside lifestyle interventions, can potentially improve MASLD treatment. Drug repurposing and new targets will advance MASLD therapy, addressing its increasing global burden. This review aims to provide a better understanding of the role of mitochondrial dysfunction in MASLD and identify more effective preventive and treatment strategies.