Metabolic dysfunction-associated steatotic liver disease (MASLD) encompasses a spectrum of liver conditions ranging from simple steatosis to the more severe metabolic dysfunction-associated steatohepatitis (MASH). MASLD is strongly linked to insulin resistance disorders, with a high prevalence among patients with type 2 diabetes. Long-term complications include liver cirrhosis, liver cancer, and cardiovascular disease. This article elucidates the complex interplay between hypertriglyceridemia, obesity, insulin resistance, and MASLD and provides an exploration of various etiologies, including genetic predispositions and secondary factors such as diabetes, medication use, and alcohol consumption. While MASLD treatment remains an unmet need, multiple pharmacological therapies are targeting hypertriglyceridemia and MASLD, including statins, peroxisome proliferator-activated receptors (PPARs) agonists, biguanides, incretins, and emerging therapies including angiopoietin-like (ANGPTL) 3 and apolipoprotein (APO) C-III inhibitors, fibroblast growth factor (FGF) 21 analogues, and thyroid hormone receptor agonists. By examining these interconnected facets, this review offers insights into potential therapeutic strategies for MASLD and associated comorbidities.