Introduction Chronic respiratory failure in children is a significant health problem leading to tracheostomy at home following hospital discharge. Providing long-term care for children at home becomes challenging when they require complex medical treatments, placing a burden on caregivers. Objectives 1) To describe caregiver burden of children with chronic respiratory failure with tracheostomy at home, and 2) To examine the relationships between caregiving self-efficacy, social support, coping, and caregiver burden of children with chronic respiratory failure with tracheostomy at home. Design A descriptive correlational design employing Chou’s caregiver burden as the conceptual framework Methodology Through purposive sampling with inclusion criteria, the sample included 85 caregivers of children aged three months to 15 years old with tracheostomy at home, who were receiving care at a super tertiary hospital in Bangkok metropolitan area and a tertiary hospital in a northern province of Thailand from May 2022 to January 2023. The instruments used for data collection comprised the following: the personal information of caregiver and children questionnaire, the caregiver burden questionnaire, the caregiving self-efficacy questionnaire, the social support questionnaire, and the coping questionnaire. These instruments revealed content validity indices of .86, .97, .92 and .97, respectively and internal consistency reliability, with Cronbach’s alpha coefficients of .90, .95, .95 and .92, respectively. Data were analyzed using descriptive statistics and Pearson’s product-moment correlation. Results The overall caregiver burden score averaged at a moderate level (M = 2.57, SD = 0.10). Furthermore, caregivers perceived a moderate level of burden across all subscales, including physical, emotional, social, and financial burdens (M = 2.51, 2.42, 3.00 and 3.00, with SD = 0.98, 1.01, 1.15 and 1.15, respectively). Social support was at a high level (M =2.83, SD = 0.07) and revealed a significant negative correlation with caregiver burden (r = -.292, p = .007). Caregiving self-efficacy was high, while coping was at a moderate level; however, there was no significant correlation between these factors and caregiver burden (r = -.182, p = .097, and r = -.139, p = .203, respectively). Recommendation The results from this study highlighted the burden experienced by caregivers of children with chronic respiratory failure requiring tracheostomy care at home, as well as the factor related to this burden. It is necessary for healthcare providers to provide targeted training programs aimed at enhancing caregivers’ knowledge and skills in home-based child care. Additionally, offering informational and emotional support, along with providing necessary medical equipment, should be considered to alleviate caregiver burden.