Background: Cocaine use has been an extremely serious and major public health issue worldwide. The risk of cocaine addiction is terribly high leading to unintentional fatal and serious pathological complications. The emergency management of cocaine overdose might be challenging. The discussion of this review stands on evidence-based and designed elements for diagnosing and managing cocaine overdose, to aid ER physicians to provide successful management and evaluation techniques to assess cocaine toxicity issues and complications. Objectives: To provide the recent literature on diagnosing and managing cocaine overdose as an ER physician. Methodology: Comprehensive medical research was collected from PubMed/MEDLINE using these search terms ((“Cocaine "[Mesh] AND “Overdose” [Mesh] AND “Diagnosis” [Mesh] AND “Management” [Mesh])). Conclusion: ER physicians must consider taking a full history, positive clinical laboratory results, and pharmacological aspects with multidisciplinary care in order to improve patient outcomes.