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Although wildlife trade is recognized as a significant driver of biodiversity loss and zoonotic disease emergence, translating global commitments into effective prevention measures remains challenging. To address this challenge, the International Alliance against Health Risks in Wildlife Trade supported 18 transdisciplinary projects aimed at reducing zoonotic spillover risks and bridging the gaps among science, policy, and implementation. Implemented across 23 countries in Africa, Asia, and the Americas, plus one global initiative, these projects applied integrated approaches spanning social and behavioral sciences, legal reform, and pathogen surveillance. Rejecting one-size-fits-all solutions, these projects prioritized upstream prevention and tailored risk-reduction efforts to local knowledge systems, cultural values, gender roles, and governance structures. They catalyzed new cross-sectoral partnerships, strengthened local capacity, and identified entry points for policy reform and behavior change through trust-building and inclusive dialogues. Operating in complex and dynamic environments, these projects provided actionable tools for governments and communities while generating practical lessons for implementation. The synthesis of these experiences reveals that sustained change requires more than scientific evidence, it depends on enabling political environments, trusted relationships, and context-sensitive strategies. Despite persistent operational and governance barriers, the projects demonstrate that community-led, locally grounded, and coordinated approaches are both feasible and effective. This article provides an overview of these projects, outlines key lessons, and provides insights to strengthen the prevention of future pandemics at the human–animal–environment interface. By connecting local practice with global ambition, the findings support the implementation of international frameworks and advance an integrated agenda for biodiversity conservation and health security.