This study investigates the prevalence and determinants of awareness of precision medicine among a nationally representative sample of individuals with self-reported depression and anxiety in the United States." Data were obtained from the Health Information National Trends Survey (HINTS) 5, Cycle 4, which is a study administered by the National Cancer Institute and is nationally representative. The survey, conducted between February and June 2020, targeted non-institutionalized, civilian US adults aged 18 years and older. Utilizing survey-weighted logistic regression, predictors of precision medicine awareness were assessed, encompassing sociodemographic, health-related, and technological factors. Among 890 individuals with self-reported depression and/or anxiety, approximately 15.3% reported awareness of precision medicine. Participants who had a higher level of education and those who had increased health-linked social media usage were three times more likely to be aware of precision medicine compared to those who did not. Old age was also positively associated with increased awareness. The present study's findings have disclosed an alarming lack of awareness of precision medicine, particularly among mentally ill persons with anxiety or depression, in which the targeted subgroups, including individuals with lower education levels and limited health-linked social media utilization, indicated lower levels of awareness. As such, it is recommended that such disparities be tackled using customized interventions along with educational initiatives, as this is likely to improve awareness levels while also ensuring equitable and increased access to precision medicine within the context of mental health.