Despite the development of effective vaccines against SARS-CoV-2 and an encouraging start to its roll out in many countries, in the coming months and years targeted prevention strategies will still be vital for socially marginalised groups. People experiencing multiple levels of exclusion related to homelessness, drug use, sex work, migration and their intersection can be particularly vulnerable to infection and morbidity with SARS-CoV-2 and will be less likely to benefit from population-wide prevention approaches such as contact tracing and mass vaccination. The recommendation by the Joint Committee on Vaccine and Immunisation in the UK to prioritise vaccination of people experiencing homelessness and rough sleepers is welcome, but will require ongoing vaccination programmes to ensure optimal coverage as well as targeted testing in coming years. There is a high risk that individuals who are homeless or otherwise socially excluded will be unable to be vaccinated and remain vulnerable to COVID-19 infection, limiting the potential for overall UK population coverage of COVID-19 vaccination to remain below the herd immunity threshold. In this editorial, we consider existing evidence on ‘what works’ in vaccine provision and contact tracing among socially excluded populations, as well as learning from the response so far including the provision of emergency accommodation and vaccine delivery. We set out strategies for interventions and priority research questions, emphasising the importance of co-production in research and service delivery, to prevent ongoing transmission of SARS-CoV-2 and future infectious disease outbreaks.