Lee's research focuses on mathematical programming, information technology, game theory, networks, machine learning and computational algorithms for risk assessment, decision making, predictive analytics and knowledge discovery, and systems and performance optimization. She has made major contributions in advances to business operations transformation, biomedicine and clinical research, emergency response and disaster preparedness, and healthcare operations. Her homeland security work has focused on risk assessment and protection of critical infrastructures, including healthcare, supply chain and logistics, power plants, communication, and finance.