The wildlife trade has been characterized as one of the biggest risk factors in the emergence of new infectious diseases. In the shadow of COVID-19, there is growing political and scientific urgency to manage this risk. Existing studies and experiences make it clear that something must be done but are less clear on how to get it done. It is a quite different task to accumulate evidence on the presence of pathogens, their locations in the supply chain, and their spillover to new hosts than to identify effective ways to prevent and mitigate emerging disease under real-world conditions. This study sought peer-reviewed evidence on the effectiveness, acceptability, feasibility, and sustainability of risk reduction interventions for zoonotic and nonzoonotic disease emergence in the wildlife trade. An environmental scan triangulated information from a scoping review following a Preferred Reporting Items for Systematic Reviews and Meta-analysis extension for scoping review protocol, two narrative literature reviews, and key informant interviews of 26 international wildlife health experts. Existing literature has been inattentive to program implementation or evaluation studies. There was insufficient evidence to identify effective and sustainable risk management actions. Studies on the effects of social, epidemiologic, and ecologic context on intervention success was lacking, as was research using a complex systems perspective. The lack of systematic program evaluations or implementation studies leaves decision makers with insufficient evidence to select interventions likely to be acceptable, effective, and sustainable within and across the disparate context of the wildlife trade. This necessitates adaptive risk management and innovations in program implementation and evaluation to ensure evidence-based risk management.