Background: Globally, the number of illegal drug users is rising, posing mental and physical health challenges and increasing societal burdens. Despite a significant need for treatment, only about 10% of these individuals receive it worldwide, often with poor adherence. Traditional treatments, while effective, suffer from high dropout rates due to limitations. The COVID-19 pandemic has spurred the growth of digital interventions like apps and online platforms, offering flexibility and cost-effectiveness that better meet patient needs and improve engagement. However, addressing the persistently high dropout rates in these online treatments is crucial and necessitates further research. Objective: This study aimed to estimate dropout rates among adults with illicit drug use participating in digital psychosocial intervention trials, and to identify factors associated with attrition. Methods: We conducted a systematic search of five major databases for English-language randomized trials published up to January 27, 2025. A total of 40 studies (80 arms; 9,563 participants) reporting 46 dropout rate estimates were included. A random-effects model was used to calculate pooled dropout rates, with meta-regression and subgroup analyses exploring potential moderators. The study was registered on PROSPERO (CRD42024534389). Results: At post-test, the pooled dropout rate in the intervention group across 17 studies was 22.4% (95% CI: 12.4%–37.2%). Dropout was significantly associated with education level, employment status, baseline clinical diagnosis, intervention frequency, and initial medication use. During the longest follow-up (29 studies), the dropout rate was 27.9% (95% CI: 18.8%–39.3%), with marital status, recruitment source, medication frequency, and intervention modality as significant predictors. Control group dropout rates were 25.9% and 28.3%, both higher than those in the intervention group. Conclusions: This meta-analysis revealed substantial dropout among adults with illicit drug use receiving digital psychosocial interventions. Targeted modifications to intervention design may improve engagement and long-term retention. Clinical Trial: The study was registered on PROSPERO (CRD42024534389).