HIV poses a significant issue in the United States and understanding how HIV-positive populations adhere to treatments, specifically with antiretroviral therapy (ART), is vital for researchers to find approaches to improve medication adherence. This systematic review aims to explore barriers that children, adolescents, and young people (ages < 25) in the United States may face by exploring family interventions and factors influencing ART adherence. This study conducted a literature search using various databases to retrieve studies within the United States. A total of 36 studies identified family factors (n = 29) and various interventions (n = 7). Across both categories, studies indicated the critical role of family involvement in adherence outcomes. The review also identified significant barriers to ART adherence, including complex medication regimens, HIV-related stigma, and psychosocial stressors. Due to the diverse barriers, policymakers and healthcare providers should focus on a holistic approach to support ART adherence in HIV-positive youth.