Over the past two decades, countries in Latin America and the Caribbean have made substantial progress in strengthening research systems, in which the Pan American Health Organization (PAHO) Policy on Research for Health has been instrumental. Research agendas have emerged as a key mechanism to bridge national policy priorities with the production of relevant and timely evidence that is aligned with national health priorities. This paper explores the strategic role of health research agendas in aligning evidence generation with decision-making needs. Drawing on recent exercises conducted in the region, including a regional health research agenda for the Oropouche virus and the Costa Rican Social Security System (CCSS) research agenda, the paper highlights both the progress and persistent challenges in this process. A core contribution of these two examples is the introduction of the Matching Q-M tool, a decision-support resource that helps translate policy-relevant topics into well-formulated research questions and match them with appropriate methodological approaches to address them. By enhancing communication between policymakers and researchers, the potential for research agendas to inform relevant, feasible, and demand-driven studies can help to institutionalize and consolidate the role of research as a strategic lever for health equity and system improvement. In a region where the research community has made long-standing contributions, national research agendas can serve as a foundational element of more resilient, responsive, and evidence-informed health systems.