PROJECT ABSTRACT Polysubstance use is a critical public health concern. Evidence indicates that the majority of persons who use drugs engage in use of multiple substances which places them at increased risk of overdose. Despite the role of polysubstance use in the current overdose crisis, it remains an understudied and poorly understood phenomenon. To accelerate the field of polysubstance use, a “Polysubstance Use Symposium” is proposed to be held October 20-21, 2022, in New York City, New York. The central location of this major transportation hub will facilitate the attendance of local and non-local experts, including scholars from major research universities, policymakers, practitioners, and other interested stakeholders. The 1.5-day meeting includes a keynote presentation, a series of concurrent research sessions, a poster and networking reception, an early career investigator mentoring session, a thematic panel, methods workshop, and interactive funding roundtables. The overall objective of the symposium is to accelerate knowledge of polysubstance use by bringing together an interdisciplinary group of stakeholders with tremendous potential for a positive impact on the public health crisis of polysubstance use. The specific goals of the symposium are to (1) increase collaborative efforts among experts and new researchers of polysubstance use to generate new research aimed at reducing the public health crisis of polysubstance use, (2) provide a formal opportunity to disseminate cutting-edge research in the field of polysubstance use as related to three important domains: prevalence and emerging trends, treatment, and social determinants; and (3) engage polysubstance use researchers in formal networking opportunities, with an emphasis on generating opportunities for early career and underrepresented researchers. The symposium will provide actionable information to researchers of polysubstance use, increase networking among stakeholders to increase innovative research proposals and solutions, and support early career and underrepresented scholars of polysubstance use in advancing their career goals.