Purpose <p>This study investigated the impact of healthcare professional-led interventions on adherence to oral targeted therapy and identified the behavior change techniques (BCTs) underpinning the interventions.</p> Methods <p>A systematic search of MEDLINE, Embase, APA PsycInfo, CINAHL Plus, PubMed, and Web of Science up to July 2024 identified randomized controlled trials and cohort studies involving adult patients (≥ 18&#xa0;years) with cancer on oral targeted therapy receiving healthcare professional-led interventions to improve adherence. Adherence-related outcomes, including proportions of patients continuing treatments or with a medication possession ratio (MPR) ≥ 90%, were compared between intervention and control (usual care) groups. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) and heterogeneity (<i>I</i>² statistic) were reported. Differences in median time to treatment discontinuation were calculated and synthesized where applicable. Interventions were categorized using the BCT taxonomy.</p> Results <p>This review included 11 studies (1,654 patients). The pooled results for proportions of patients continuing treatment (OR 17.91; 95%CI 3.18, 100.73; <i>I</i>^<i>2</i> &lt; 0.1%) or with an MPR ≥ 90% (OR 3.67; 95%CI 1.98, 6.80; <i>I</i>^<i>2</i> &lt; 0.1%) showed a significantly favorable outcome in the intervention group compared to the control group. In two studies, the median time to treatment discontinuation was longer in the intervention group than in the control group. The most commonly used BCTs were “credible source” (<i>n</i> = 11), “problem-solving” (<i>n</i> = 9), “instruction on how to perform a behavior” (<i>n</i> = 9), and “pharmacological support” (<i>n</i> = 8).</p> Conclusion <p>Despite limited evidence, healthcare professional–led interventions significantly improve treatment adherence. Future studies should tailor strategies for individual needs and apply BCTs in designing effective interventions.</p> <p>PROSPERO registered: no. CRD42024571808.</p>