Background: The use of home health care (HHC) is increasing worldwide. This may have an impact not only on patients and their caregivers’ health but on care resource utilization and costs. We lack information on the impact of HHC on the broader dimensions of health status and care resource utilization. More understanding of the longitudinal HHC impact on HHC patients and caregivers is also needed. Moreover, we know little about the synergy between HHC and social care. Therefore, the present study aims to observe longitudinal changes in health, care resource utilization and costs and caregiving burden among HHC recipients and their caregivers in Taiwan. Methods: A prospective cohort study “Home-based Longitudinal Investigation of the Multidisciplinary Team Integrated Care (HOLISTIC)” will be conducted and 600 eligible patient-caregiver dyads will be recruited and followed with comprehensive quantitative assessments during six home investigations over two years. The measurements include physical function, psychological health, cognitive function, wellbeing, shared decision making and advance care planning, palliative care and quality of dying, caregiving burden, continuity and coordination of care, care resource utilization, and costs. Discussion: The HOLISTIC study offers the opportunity to comprehensively understand longitudinal changes in health conditions, care resource utilization and costs and caregiving burden among HHC patients and caregivers. It will provide new insights for clinical practitioners and policymakers. Trial registration: ClinicalTrials.gov Identifier is NCT04250103 which has been registered on 31st January 2020.