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Illicit Wildlife Trade (IWT) is a serious global crime that negatively impacts biodiversity, human health, national security, and economic development. Many flora and fauna are trafficked in different product forms. We investigate a network interdiction problem for wildlife trafficking and introduce a new model to tackle key challenges associated with IWT. Our model captures the interdiction problem faced by law enforcement impeding IWT on flight networks, though it can be extended to other types of transportation networks. We incorporate vital issues unique to IWT, including the need for training and difficulty recognizing illicit wildlife products, the impact of charismatic species and geopolitical differences, and the varying amounts of information and objectives traffickers may use when choosing transit routes. Additionally, we incorporate different detection probabilities at nodes and along arcs depending on law enforcement’s interdiction and training actions. We present solutions for several key IWT supply chains using realistic data from conservation research, seizure databases, and international reports. We compare our model to two benchmark models and highlight key features of the interdiction strategy. We discuss the implications of our models for combating IWT in practice and highlight critical areas of concern for stakeholders.