Current treatment paradigms for metabolic dysfunction-associated steatohepatitis (MASH) are based primarily on dietary restrictions and the use of existing drugs, including anti-diabetic and anti-obesity medications. Given the limited number of approved drugs specifically for MASH, recent efforts have focused on promising strategies that specifically target hepatic lipid metabolism, inflammation, fibrosis, or a combination of these processes. In this review, we examined the pathophysiology underlying the development of MASH in relation to recent advances in effective MASH therapy. Particularly, we analyzed the effects of lipogenesis inhibitors, nuclear receptor agonists, glucagon-like peptide-1 (GLP-1) receptor (GLP-1R) agonists, fibroblast growth factor mimetics, and combinatorial therapeutic approaches. We summarize these targets along with their preclinical and clinical candidates with the ultimate goal of optimizing the therapeutic prospects for MASH.