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Social determinants have been increasingly implicated in accelerating HIV vulnerability, particularly for disenfranchised communities. Among these determinants, neighborhood factors play an important role in undermining HIV prevention. However, there has been little research comprehensively examining the impact of neighborhood factors on HIV care continuum participation in the US. To address this, we conducted a systematic review (PROSPERO registration number CRD42022359787) to determine neighborhood factors most frequently associated with diminished HIV care continuum participation. Peer-reviewed studies were included if published between 2013 – 2022, centralized in the US, and analyzed a neighborhood factor with at least one aspect of the HIV care continuum. The review was guided by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) protocol. Study quality was guided by LEGEND (Let Evidence Guide Every New Decision) evaluation guidelines. Systematic review analysis was conducted using Covidence software. There were 3,192 studies identified for initial screening. Forty-four were included for review after eliminating duplicates, title/abstract screening, and eligibility assessment. Social and economic disenfranchisement of neighborhoods negatively impacts HIV care continuum participation among persons living with HIV. In particular, five key neighborhood factors (socioeconomic status, segregation, social disorder, stigma, and care access) were associated with challenged HIV care continuum participation. Race moderated relationships between neighborhood quality and HIV care continuum participation. Structural interventions addressing neighborhood social and economic challenges may have favorable downstream effects for improving HIV care continuum participation. [ABSTRACT FROM AUTHOR]