Hyperlipidemic acute pancreatitis (HLAP) is triggered by severe disturbances in lipid metabolism, progresses rapidly, and is associated with a high risk of complications. Its pathogenesis involves multiple mechanisms, including chylomicron accumulation and free fatty acid toxicity, activation of inflammatory pathways, and disruption of intracellular calcium homeostasis. Recent studies have shown that polymorphisms in lipid metabolism-related genes can influence HLAP susceptibility, disease severity, and lipid-lowering drug efficacy by regulating lipoprotein metabolism, fatty acid oxidation, and inflammatory responses. This article systematically reviews the associations between major lipid metabolism gene polymorphisms and HLAP/hypertriglyceridemia, gene-gene and gene-environment interactions, and the potential impact of these polymorphisms on the therapeutic responses to fibrates, statins, and PCSK9 inhibitors. It also discusses the current status and challenges of genotype-based individualized prevention and treatment strategies, aiming to provide a theoretical basis and future directions for precision screening and personalized management of HLAP.