The opioid epidemic is a significant public health crisis and prescription opioids are often used to manage chronic pain, despite questionable long-term efficacy. Furthermore, co-substance (mis)use is also common among individuals with chronic pain who use opioids. Alcohol has been consistently used to manage chronic pain, partly due to its acute analgesic properties. Cannabis has also recently garnered attention in the context of pain management, though research examining its efficacy for pain has produced mixed results. Nevertheless, there is accumulating evidence that concurrent substance co-use is positively associated with use and misuse of additional substances, particularly among individuals with chronic pain. Thus, the goal of this study was to examine the main and interactive effects of alcohol use problems and cannabis use problems in relation to opioid misuse among adults with chronic pain who use opioids.