The chapter explores the intricate interactions between apolipoprotein E (ApoE) isoforms and mercury intoxication, emphasizing the molecular and clinical dimensions of this interplay. ApoE, a critical glycoprotein in lipid metabolism and neuronal homeostasis, exists in three primary isoforms - ApoE2, ApoE3, and ApoE4 - each influencing physiological and pathological outcomes differently. Mercury exposure, particularly methylmercury (MeHg), induces oxidative stress, neuroinflammation, and cardiovascular dysfunction, with ApoE isoforms modulating these effects. ApoE4 carriers display heightened vulnerability to mercury-induced neurotoxicity and endothelial dysfunction due to reduced antioxidant capacity and increased pro-inflammatory propensities. The chapter synthesizes evidence from experimental animal models and observational studies, highlighting genetic variability in mercury susceptibility across populations and the clinical significance of ApoE polymorphisms in modulating mercury toxicity. Additionally, scientometric analyses were conducted based on available literature indexed in one of the most prominent scientific databases, aiming to identify current research trends in the field. By integrating biochemical, epidemiological, and genetic perspectives, this work aims to consolidate existing knowledge and propose new avenues for research and intervention in mercury-related toxicology.