AbstractThis study utilized a sequential explanatory mixed-methods design in understanding the secondary system of therapeutic alliance from the perspectives of parents and caregivers of children with autism. In the quantitative phase, data from the accomplished questionnaires of 124 parent–caregiver dyads were collected and analyzed. Four factors extracted from the literature: treatment attitude, treatment compliance, level of stress, and perceived autism severity were examined as possible predictors of parent–therapist alliance, caregiver–therapist alliance, and parent–caregiver alliance. In the qualitative phase, eight parent–caregiver dyads (who both scored high in their alliance with therapist, alliance with each other, treatment attitude, treatment compliance, and level of stress) were interviewed to probe on their experiences of alliance-building, parenting, and caregiving. The integration of both quantitative and qualitative data led to the formulation of a conceptual framework that explains how the factors influence the secondary system of therapeutic alliance. These findings emphasize that tapping into the personal experiences of parents and caregivers can help in identifying what they value in a working, therapeutic relationship. Moreover, communication, skills training, and feedback among therapists, parents, and caregivers are essential to enhance positive attitude toward treatment, promote compliance to treatment recommendations, and address sources of personal stress. Nevertheless, this study calls for future studies to build into the factors associated with the systemic therapeutic alliance and to implement intervention programs that may target issues relating to attitude toward treatment, compliance to treatment, and experience of parental and caregiver stress.