Aim: Non-medical use of prescription opioids, such as tramadol, is a major health concern globally. In Sweden, non-medical tramadol use among young people is widely recognized. This study explores the central components that characterize drug use trajectories among young people with experiences of problematic tramadol use. Methods: 24 qualitative interviews were conducted with 13 young people (aged 19–24) with self-reported experiences of problematic tramadol use. The concepts of drug, set, and setting from Zinberg’s theoretical framework were applied to explore significant aspects of their drug use trajectories. Findings: Four themes corresponding to different stages in the young people’s drug use trajectories, were identified: (1) initiating tramadol use; (2) developing continuous tramadol use; (3) expanding the drug repertoire and; (4) starting to lose control. Overall there was a progression toward more severe drug use over time, where self-medication and dependence dynamics, as well as peer influence and other environmental factors were significant. Conclusion: The study demonstrates that the drug use trajectories of young people with problematic tramadol use involve a complex interaction between the drugs’ effects, personal circumstances, and environmental factors. Increasing the understanding of this process can be helpful in improving both preventive and therapeutic measures for this target group.