Parental domestic violence and abuse (DVA), mental ill-health (MH), and substance misuse (SU) are three public health issues that tend to cluster within families, risking negative impacts for both parents and children. Despite this, service provision for these issues has been historically siloed, increasing the barriers families face to accessing support. Our review aimed to identify family focused interventions that have combined impacts on parental DVA, MH, and/or SU. We searched 10 databases (MEDLINE, PsycINFO, Embase, CINAHL, Education Research Information Centre, Sociological Abstracts, Applied Social Sciences Index & Abstracts, ProQuest Dissertations and Theses Global, Web of Science Core Collection, and Cochrane Central Register of Controlled Trials) from inception to July 2021 for randomised controlled trials examining the effectiveness of family focused, psychosocial, preventive interventions targeting parents/carers at risk of, or experiencing, DVA, MH, and/or SU. Studies were included if they measured impacts on two or more of these issues. The Cochrane Risk of Bias Tool 2 was used to quality appraise studies, which were synthesised narratively, grouped in relation to the combination of DVA, MH, and/or SU outcomes measured. Harvest plots were used to illustrate the findings. Thirty-seven unique studies were identified for inclusion. Of these, none had a combined positive impact on all three outcomes and only one study demonstrated a combined positive impact on two outcomes. We also found studies that had combined adverse, mixed, or singular impacts. Most studies were based in the U.S., targeted mothers, and were rated as 'some concerns' or 'high risk' of bias. The results highlight the distinct lack of evidence for, and no 'best bet', family focused interventions targeting these often-clustered risks. This may, in part, be due to the ways interventions are currently conceptualised or designed to influence the relationships between DVA, MH, and/or SU. Trial registration: PROSPERO registration: CRD42020210350.