This systematic review compared the efficacy of interventions to usual care on adherence to oral anticancer regimens.Embase®, PubMed®, and CINAHL® were searched for eligible comparative studies published between January 2000 and May 2021. Outcomes of interest included adherence, cancer-related morbidity, quality of life, patient satisfaction, and other patient-specific outcomes.Reviewers assessed risk of bias using the Cochrane Risk of Bias 2 tool and Risk of Bias in Nonrandomized Studies of Interventions. Certainty of evidence was assessed using the GRADE framework.Risk assessment, ongoing or periodic assessment, proactive follow-up, motivational interviewing, or structured programs may improve adherence. Education or coaching interventions may improve or have little to no effect on adherence. Technological interventions may improve adherence, but interactive compared to noninteractive technology may have little to no effect.As more cancer treatments move to oral formulations, work remains to identify the most effective interventions to support people receiving oral anticancer regimens.