Background: Appropriate knowledge about Human Immunodeficiency Virus is critical for preventing transmission and managing the disease. Lack of knowledge can seriously hinder treatment adherence. Family support is also crucial, as emotional and practical assistance from families improves psychological well-being, motivation, and creates a supportive environment for acceptance of the condition. Purpose: This study explores the association between knowledge and family support towards medication adherence among people living with HIV. Methods: An observational cross-sectional design was used. A total of 150 HIV patients from two public health centers were selected using convenience sampling. Data were collected using demographic questionnaire, the Indonesian versions of the HIV Knowledge Questionnaire (HIV-KQ18), the Family Support Scale, and the Morisky Medication Adherence Scale (MMAS), and analyzed using Sommer test correlation. Results: A weak significant relationship was found between knowledge and medication adherence (p = 0.003; contingency coefficient = 0.231). Similarly, family support was weak significantly associated with medication adherence (p = 0.0001; contingency coefficient = 0.327). Conclusion: This study identified weak significant links between knowledge and medication adherence, and between family support and medication adherence. Implications for Nursing: Nurses should routinely assess HIV knowledge and family support to provide tailored education and family-inclusive care. Nursing programs, future research, and healthcare policies must prioritize family-centered approaches and nurse-led support initiatives to improve medication adherence.