The Caribbean has long been an under-represented geographical region in the field of genomics research. Such under-representation may result in Caribbean people being underserved by precision medicine and other public health benefits of genomics. A collaboration among regional and international researchers aims to address this issue through the H3ECaribbean project (Human Heredity, Environment, and Health in the Caribbean), which builds on the lessons and success of H3Africa. The Caribbean project aims to target issues of social justice by encouraging the inclusion of diverse Caribbean communities in genomics research. This paper explores a framework for the ethical and socially acceptable conduct of genomics research in the Caribbean, taking account of the cultural peculiarities of the region. This is done in part by exploring research ethics issues identified in indigenous communities in North America, Small Island Developing States, and similar endeavours from the African continent. The framework provides guidance for interacting with local community leaders, as well as detailing steps for obtaining informed consent of all participants. Specifically, the authors outline the methods to ensure effective interaction and enforce full transparency with study participants to combat historical neglect when working with under-represented communities in the Caribbean.