The number of people in the US with opioid abuse exceeds two million, and the total cost is approximately $100B per year. There is a need for smart interventions that can lead to better outcomes for patients and reduce the need for healthcare resources. In this study, the authors present three smart interventions for patients: (a) mobile reminders, (b) electronic monitoring, and (c) composite intervention. More specifically, the authors present a design approach for smart interventions and operationalize the interventions. They have developed an analytical model for evaluating interventions. Interventions are cost-effective for higher values of intervention effectiveness, hospital, and emergency room cost. However, with quality-of-life (QoL) improvement, cost-effectiveness improves significantly. The authors also explored the use of financial incentives for increasing the adoption of interventions. These results will help patients, healthcare professionals, decision-makers, and family members to choose the most suitable intervention to address opioid abuse.