Background: Whilst the majority of young people succeed in education and make a positive transition to the world of work and adult life, recent statistics identify that youth comprise 40% of the world's unemployed, equating to nearly 75 million individuals. These numbers are associated with both decreased economic activity and adverse well-being, with accompanying social, health and financial costs. As a result, a wide range of providers have implemented interventions targeting this population; however, their relative effectiveness is unknown. This is exacerbated by a diverse literature base, the delivery of provision and policy across multiple sectors and disparate approaches to programme evaluation. Methods and design: We will undertake a systematic review of interventions targeting youth not in employment, education or training (NEET) populations. Only randomised and non-randomised controlled trials will be included. The objectives of the review will be to: (i) systematically review, synthesise and quality appraise experimental evidence on the effects of interventions with NEET young people, (ii) estimate effects on current NEET status, well-being and other relevant psychological and behavioural outcomes, (iii) investigate potential variation in intervention effects among sub-groups stratified by pre-trial duration of current status, socioeconomic status, gender, sub-classifications of NEET individuals and intervention components (e.g. type, frequency, duration, provider and setting) and (iv) assess the robustness of results in separate sensitivity analyses that exclude studies with higher risk of bias (e.g. in terms of study quality) or follow-up length. A rigorous literature search of English language publications post-1990 will be conducted using the following electronic databases: Medline, Embase, PsycINFO, ERIC, EPPI-Centre (Bibliomap), Social Science Citation Index, British Education Index, Conference Proceedings Index, Dissertation Abstracts, Popline and grey literature collections (e.g. GLADNET). These database searches will be supplemented with hand searching, requests for unpublished literature and website searches. Discussion: A report and executive summary will be developed by the research team with input from consultant stakeholders to aid translation of the findings into practice. The research will be disseminated at national and international conferences and submitted for peer-reviewed publication.