Chronic pain is a major public health issue that frequently leads to analgesic opioid prescriptions. These prescriptions could cause addiction issues in high-risk patients with associated comorbidities, especially those of a psychiatric, addictive, and social nature. Pain management in dependent patients is complex and is yet to be established. By combining the views of professionals from various specialties, we conducted an integrative review on this scope. This methodology synthesizes knowledge and results of significant practical studies to provide a narrative overview of the literature. The main results consisted in first proposing definitions that could allow shared vocabulary among health professionals regardless of their specialties. Next, a discussion was conducted around the main strategies for managing prescription opioid dependence, as well as pain in the context of opioid dependence and associated comorbidities. As a conclusion, we proposed to define the contours of holistic management by outlining the main guidelines for creating a multidisciplinary care framework for multi-comorbid patients with chronic pathologies.