This study examines the risks posed by the on-site reactivity of hazardous chemicals, focusing on high-risk accident scenarios and response system improvements. Using cases like TATP and VX, it analyzes the accessibility and combination potential of precursor chemicals that are not inherently hazardous but can become highly dangerous under specific conditions. Scenario-based qualitative risk assessments reveal critical gaps in South Korea’s current safety management, including insufficient anticipatory regulations, limited detection capabilities for reactively synthesized agents, and fragmented inter-agency coordination. The study highlights the need for a proactive, integrated approach incorporating real-time precursor tracking, advanced detection technologies, and joint scenario-based response training. By shifting from static substance control to risk-based preparedness, this research offers strategic recommendations for enhancing chemical accident prevention and response in complex facility environments.