<p>Trace elements are chemical elements required in small quantities for normal physiological and biochemical functions in biological systems. These elements are grouped as essential (Fe, Zn, Cu, Mn etc.) and non-essential elements (Al, As, Pb, Hg etc.). Essential trace elements play crucial roles in maintaining the physiological and metabolic cellular operations of biological systems and are important enzymatic co-factors. On the other hand, non-essential trace elements have no known physiological functions in biological systems and produce toxicity on bioaccumulation. This review provides a detailed analysis of Arsenic (As), which is a potential non-essential metalloid and has adverse global health effects. We have discussed the multifaceted molecular mechanisms of arsenic toxicity such as genotoxicity, induction of oxidative stress by reactive oxygen species (ROS) species production, epigenetic dysregulation and pro-inflammatory signaling cascade. Special attention is placed on intersection of metabolic biotransformation and systemic toxicity, particularly the “depletion” of methyl donor during process of biotransformation of arsenic. Moreover, the study assesses epidemiological profile of arsenicosis, distinguishing key biomarkers, indicative features of arsenicosis and synergistic risk linked with variation in exposure. Finally, we focused on chelation therapies, detoxification strategies and potential intervention measures, furnishing a quantitative framework for risk evaluation and implementation of effective public health policies.</p>