Research has consistently shown that individual, interpersonal, community, and structural factors influence the degree to which individuals’ access and utilize health care services, and these factors may play a role in explaining racial and ethnic differences in health care outcomes. Differences in human immunodeficiency virus (HIV) prevalence and treatment between Latinx adults and White adults in the U.S. must be considered in the context of these factors. However, much of the existing research connecting these factors and HIV/acquired immonodeficiency sydrome (AIDS) outcomes in Latinxs remains disparate, limited in scope, and has yet not been applied to the use of biomedical HIV preventions. The following systematic literature review examined research related to preexposure prophylaxis (PrEP) in Latinx sexual minority men (SMM) to build a structural-ecological framework of the existing research, while identifying gaps in the literature and areas for future research. We searched two electronic databases using a systematic review protocol, screened 71 unique records, and identified 23 articles analyzing data from Latinx SMM and intended and/or actual PrEP-use in the U.S. Based on the present review, disparities in PrEP uptake by Latinx SMM could be explained, in part, by examining how all levels of the structural-ecological framework uniquely contributes to how Latinx SMM engage with HIV prevention measures and come to understand PrEP. It is clear from the existing literature base that some of the most prominent barriers deterring Latinx SMM from seeking PrEP services are the lack of information surrounding PrEP and HIV/gay stigmas. However, higher order structural-level risks can facilitate or reduce access to PrEP. We propose a structural-ecological model to help visualize multilevel domains of unique stressors that limit the implementation of PrEP among Latinxs. At this stage, the available literature provides little guidance beyond suggesting that culturally adapted interventions can be effective in this population. The model developed here provides that needed specificity regarding targeted interventions that will fit the needs of this population. (PsycInfo Database Record (c) 2022 APA, all rights reserved)