Wildlife trafficking and other commodities associated with environmental crimes traded across the borders of the Greater Mekong Subregion (GMS) carry direct or indirect risks for biological threats. Outbreaks associated with these threats can have devasting implications for human populations as well as for farmed or native animal and plant populations. Although the links between environmental crimes and biological threats are obvious, we see two disconnected responses which limits the ability to tackle both the crime and the risks of biological threats. On one hand, there are efforts to improve law enforcement prioritisation and capability to disrupt transnational organised crime. On the other hand, we see increasing resources channelled through a One Health framework that aim to improve early warning surveillance of emerging infectious disease with a focus on diseases that can affect livestock or zoonotic diseases that can affect human health. The COVID-19 pandemic has provided a unique opportunity to explore alternative strategies, particularly the need to expand the operational definition of One Health to usher in more joined up partnerships between security sector personnel and human and animal health personnel working along borders of the GMS. This policy commentary draws on a literature review and informal stakeholder discussions conducted in preparation for on ongoing formal research project. This commentary provides policy and program considerations for improving both the enforcement of environmental crimes and early warning biological threat surveillance, preparedness and response in the Greater Mekong Subregion.