While the Association of Southeast Asian Nations (ASEAN) and the European Union (EU) relaunched negotiations on ASEAN-EU FTA in 2017, few signs have indicated significant progress in trade talks and EU has been prompted to pursue, in parallel, bilateral free trade agreements (FTAs) with individual ASEANMembers States as building blocks for the region-to-region megaproject. The underlying divergence in economic, political, historical, and social dimensions between ASEAN and EU has continued to condition bi-regional negotiations, and issues of sanitary and phytosanitary (SPS) are of particular importance given the large inter-regional agri-food trade and inherent tensions embedded in SPS measures that are adopted to strike a balance between trade liberalization and public health. Whether and how the two blocs can reconcile different interests and policy agendas in shaping SPS cooperation under the prospective FTA merits in-depth examination. This article analyses the trajectory and dynamics in ASEAN-EU SPS cooperation. It assesses the SPS Chapters of the EUSingapore and EU-Vietnam FTAs, drawing on their relevance to and implications for region-to-region development. Lastly, this article highlights various bottom-up SPS cooperation initiatives between the two—due to EU’s technical assistance, and more critically, ambition to export its normative paradigms globally—emphasizing their role as catalyst for deeper region-to-region SPS cooperation.