As Southeast Asia (SEA) is characterized by high human and domestic animal densities, growing intensification of trade, drastic land use changes and biodiversity erosion, this region appears to be a hotspot to study complex dynamics of zoonoses emergence and health issues at the Animal-Human-Environmental interface. Zoonotic diseases and environmental health issues can have devastating socioeconomic and wellbeing impacts. Assessing and managing the related risks implies to take into account ecological and social dynamics at play, in link with epidemiological patterns. The implementation of a One Health (OH) approach in this context calls for improved integration among disciplines and improved cross sectoral collaboration, involving stakeholders at different levels. For sure, such integration is not achieved spontaneously, implies methodological guidelines and has transaction costs. We explore pathways for implementing such collaboration in SEA context, highlighting the main challenges to be faced by researchers and other target groups involved in OH actions. On this basis, we propose a conceptual framework of OH integration. Throughout 3 components (field-based data management, professional training workshops and higher education), we suggest to develop a new culture of networking involving actors from various disciplines, sectors and levels (from the municipality to the Ministries) through a participatory modelling process, fostering synergies and cooperation. This framework could stimulate long-term dialogue process, based on the combination of case studies implementation and capacity building. It aims for implementing both institutional OH dynamics (multi-stakeholders and cross-sectoral) and research approaches promoting systems thinking and involving social sciences to follow-up and strengthen collective action.