Acute and chronic problems related to alcohol, drugs, and self-harm are important public health challenges and are compounded by socioeconomic inequalities. People with substance use disorders or mental ill health, or both, are attended to by ambulance and emergency departments at higher rates than the general population and their outcomes are often poor, with mortality ranging from 5% to 15% within 1 year of receiving emergency care. There is a need to better understand presentations to emergency departments and opportunities for intervention. In this Viewpoint, we discuss the need for a holistic understanding of emergency care interactions linked to alcohol, drugs, and self-harm, and the urgent need for integrated research. We propose an integrated public health and emergency care approach to tackle this issue. Importantly, future research should address the underlying social and environmental determinants of substance misuse and self-harm. When developed in collaboration with people with lived or living experience, such an integrated approach to care and research has the potential to reduce harm, improve quality of life, prevent premature mortality, and inform policy and practice.