Illicit drug overdose is a public health issue that leads to significant morbidity and mortality. In order to reduce the harm associated with substance use, emergent issues related to substances and substance use must be addressed in a timely manner, which requires inter-sectoral collaboration. We describe the British Columbia Drug Overdose and Alert Partnership, an innovative collaborative model of stakeholders who work in prevention, harm reduction, treatment and enforcement related to psychoactive substance use. We describe the formation, purpose, stakeholders, and operation of the partnership and resultant public health surveillance system. We use the example of fentanyl-associated overdoses and deaths to describe the attributes that make the system effective. These include timeliness, flexibility, acceptability and costs. This model of inter-sectoral collaboration and surveillance can be applied to other organizations involved in assessing and responding to drug-related harms.