Residence in socioeconomically disadvantaged neighborhoods and individual sociodemographic conditions contribute to worse heart failure (HF) outcomes and may influence HF self-care. However, associations between neighborhood disadvantage, socioeconomic conditions, and HF self-care are unclear. The purpose of this secondary analysis was to investigate whether neighborhood disadvantage and individual socioeconomic conditions predicted worse HF self-care. This study was a secondary analysis of baseline data from a mixed-method study of 82 adults with HF. Participant zip codes were assigned a degree of neighborhood disadvantage using the Area Deprivation Index. Those in the top 20% most disadvantaged neighborhoods (Area Deprivation Index ≥ 80) were compared with those in the least disadvantaged neighborhoods. The Self-Care of Heart Failure Index was used to measure self-care maintenance and monitoring. Multiple linear regression was conducted. Of all participants, 59.8% were male, 59.8% were persons of color, and the mean age was 64.87 years. Residing in a disadvantaged neighborhood and living alone predicted worse HF self-care maintenance and monitoring. Having no college education was also a predictor of worse HF self-care maintenance. Although persons of color were more likely to reside in disadvantaged neighborhoods, race was not associated with HF self-care. Residing in a disadvantaged neighborhood and living alone may be important risk factors for worse HF self-care. Differences in self-care cannot be attributed solely to the individual sociodemographic determinants of race, gender, age, annual household income, or marital status. More research is needed to understand the connection between neighborhood disadvantage and HF self-care.