Contingency management (CM), which involves the delivery of incentives upon meeting behavioral goals, has the potential to improve substance use treatment outcomes. The intervention allows for flexibility through numerous modifiable components including changes to incentive magnitude and schedule, target behavior, and intervention structure. Unfortunately, numerous changes in the substance use landscape have occurred in the past 10 to 15 years: Substances are more potent, overdose risk has increased, new substances and methods of use have been introduced, and substance classes are increasingly being intentionally and unintentionally mixed. These developments potentially undermine CM outcomes. We explored recent substance use changes due to legislative, regulatory, social, and economic factors for four substance classes: stimulants, opioids, tobacco, and cannabis. We discuss potential adjustments to the modifiable components of CM for future research in response to these changes. By continually adapting to the shifting substance use landscape, CM can maintain optimal efficacy.