Brain tumor patients experience physical, psychological, social, and cognitive changes. These changes are challenging for both the patients and their families. These patients and their families need to adapt together on the cancer treatment path. This study aimed to identify the factors affecting adaptation in families of adult patients with brain tumors. A quantitative, cross-sectional study of 165 families of adult patients with primary brain tumors was conducted using a self-administered questionnaire. Partial least squares structural equation modeling was used to test a hypothetical model. The results showed that family stress, family functioning, and family resources influenced on family adaptation in families of adult patients with primary brain tumors. Among these factors, family resources were identified to be the strongest factor associated with family adaptation. The results of this study may be utilized as a theoretical basis in nursing to improve the family adaptation of patients with brain tumors. Regarding nursing practices, the results suggest that nurses should provide family-centered nursing interventions and promote family resources to help brain tumor patients and their families to adapt.