The Assessing Economic Transitions (ASSET) study was established to identify relationships between economic engagement, health and well-being in inner-city populations given that research in this area is currently underdeveloped. This paper describes the objectives, design, and characteristics of the ASSET study cohort, an open prospective cohort which aims to provide data on opportunities for addressing economic engagement in an inner-city drug-using population in Vancouver, Canada. Participants complete interviewer-administered surveys quarterly. A subset of participants complete nested semi-structured qualitative interviews semi-annually. Between April 2019 and May 2022, the study enrolled 257 participants ages 19 years or older (median age: 51; 40% Indigenous, 11.6% non-Indigenous people of colour; 39% cis-gender women, 3.9% transgender, genderqueer, or two-spirit) and 41 qualitative participants. At baseline, all participants reported past daily drug use, with 27% currently using opioids daily, and 20% currently using stimulants daily. In the three months prior to baseline, more participants undertook informal income generation (75%) than formal employment (50%). Employed participants largely had casual jobs (42%) or jobs with part-time/varied hours (35%). Nested qualitative studies will focus on how inner-city populations experience economic engagement. The resulting evidence will inform policy and programmatic initiatives to address socioeconomic drivers of health and well-being.