Work-related stress in nursing is widely acknowledged. This integrative review was undertaken to systematically identify and appraise the causes of work-related stress experienced by registered nurses working with children at home. Ten studies were included, eight of which focused solely on the experiences of nurses providing palliative and end of life care at home for children. One study focused on the experiences of newly qualified nurses and one on the experiences of nurses caring for sick children at home at different stages within their care trajectory. Stress was experienced by nurses caring for children at home and identified and acknowledged within all included studies. Recurrent themes reported in the literature that contributed to work-related stress were, provision of out of hours care, challenge of developing and maintaining skills (clinical and non-clinical), ambiguity of roles and relationships (professional team and child and family), lack of resources, emotional toll, and lack of staff support. The causes of work-related stress highlighted in this review need to be proactively addressed; thus, providing an opportunity to improve the working experiences of nurses improve job satisfaction and overall well-being. A recommendation from this integrative review is for workplaces to identify and invest in effective strategies to prevent or reduce work-related stress.