<p>Here, we explore the operational challenges of One Health-related research that focuses on disease ecology, emphasizing the need to understand bridging disciplines of ecology and epidemiology. While epidemiology considers the distribution and determinants of health in populations, ecology situates biological processes of interacting organisms within broader environmental and evolutionary contexts. Disease ecology emerges as a discipline, highlighting hosts–pathogens–environment interactions and bridging gaps between epidemiology and ecology. We discuss persistent barriers to the advance of disease ecology, such as disciplinary siloes, differing methodologies, and lack of incentives that continue to hinder collaboration despite increasing awareness of the importance of disease ecology research. Integration offers benefits for epidemiology and ecology: improved understanding of prediction uncertainty, stronger evidence, and more impactful applications across veterinary and public health, and biological conservation. We list priority pathways in cross-training and high-level implementation approaches to advance disease ecology and realize the aspirational goals of One Health.</p>