Substance use remains a robust predictor of HIV infection, as well as a serious impediment to progress across the HIV care continuum for people living with HIV. As such, the careful design and implementation of interventions uniquely tailored to target substance use and HIV care behaviors remain paramount. A necessary step in these efforts is to understand the extent to which HIV care interventions have been efficacious in helping people who use substances progress across the HIV care continuum. Using PubMed and ProQuest databases, we performed a systematic review of randomized trials of HIV care continuum interventions among people who use substances published between 2011 and 2021, the treatment-as-prevention era. Existing systematic reviews and studies in which less than half of those sampled reported substance use were excluded. We identified ten studies (total N=5410; range: 210-1308), nine of which intentionally targeted substance-using populations. Four of these studies involved use of at least one of several substances, including alcohol, opioids, stimulants, and/or marijuana, among others; three involved injection drug use only; one involved methamphetamine use only; and one involved alcohol use only. One study targeted a population with incidental substance use, which involved use of alcohol, injection drug use, and non-injection drug use. Viral suppression was targeted in 8/10 studies, followed by uptake/initiation of antiretroviral therapy (ART; 6/10), ART adherence (6/10), retention to care (4/10), and linkage to care (3/10). For each outcome, intervention effects were found in roughly half of the studies in which a given outcome was assessed. Mediated (2/10) and moderated (2/10) effects were minimally examined. The diversity of substances used in and across studies, as well as other characteristics that varied across studies, prevented broad deductions or conclusions about the amenability of specific substances to intervention. Moreover, study quality was mixed due to varying attrition and assessment measures (self-report vs biological/clinical). More coordinated, comprehensive, and targeted efforts are needed to disentangle intervention effects on HIV care continuum outcomes among populations using diverse substances.