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This integrative review aimed to synthesize factors related to family functioning in families living with children with thalassemia. CINAHL, PsycINFO, PubMed, and Scopus databases were searched for articles published from 2008 to 2019. Eleven studies involving 1,613 participants were included. The five factors identified comprised spirituality, illness belief, health literacy, social interaction and communication, and social and family support. The factor regarding social and family support was a significant factor resulting in a healthy level of family functioning. Family was the primary support system for children living with thalassemia and their whole family. Interestingly, illness belief, spirituality and magic as a source of family power, could lessen the burden and allow a stronger sense of control to transcend through difficult times. These five factors should be integrated in interventions designed to enhance family functioning. However, different cultures in each region should be considered while planning for intervention to enhance family functioning.