Sexual and gender minority Hispanics/Latinxs (henceforth: Latinxs) continue to be disproportionately impacted by HIV/AIDS in the U.S. Pre-exposure prophylaxis (PrEP) is a biomedical prevention approach which holds significant promise for at risk and vulnerable populations. We discuss barriers and facilitators to uptake of PrEP among sexual and gender minority Latinxs living in the U.S. through an ecosocial lens that takes into account structural, community, and individual contexts. The impact of immigration status on PrEP uptake emerges as a major and recurrent theme that must be understood and addressed by HIV prevention programs aiming to promote an inclusive strategy for sexual and gender minority Latinxs living in the U.S.