After highlighting the latest developments in the One Health approach, the focus shifts to the need for a holistic perspective for its effective implementation enabling us to understand and tackle the causes of current and emerging transnational challenges affecting the health of humans, animals, plants and the environments. This is pursued by promoting integration with the multidisciplinary fields of Global Health and Planetary Health, pointing to their problems of definitions and approach. However, moving beyond a purely biomedical and ecological framing of One Health requires engaging with the political and economic determinants that shape health outcomes. The “Structural One Health” approach, for example, investigates the “causes of the causes” of pandemics, highlighting how trade policies, global financial flows and corporate power drive ecological degradation, intensification of animal production, and ultimately influence human wellbeing. Integrating One Health with Global Health and Planetary Health thus implies not only interdisciplinary collaboration, but also critical reflection on the economic paradigms and power structures that underpin contemporary global health crises.