Systemic exposure to allergens resulting in a cutaneous eruption is known as systemic contact dermatitis (SCD). Once sensitization occurs, varying exposures to antigens via multiple routes (including transepidermal routes, intravenous or intramuscular routes, inhalation, and ingestion) can result in systemic flare. This article highlights the different categories of common contactants, metals, medications, and plants, exposure to which leads to SCD. A comprehensive approach that takes into account all possible routes of exposure is essential in diagnosing SCD and in helping patients successfully avoid their allergens.