Background <p>Informal caregivers may face challenges, especially during the pre-transplant phase. We have learned about the challenges faced by informal caregivers during hematopoietic stem cell transplantation; there is a lack of consensus about the challenges faced by them before transplantation. We identified the psychosocial well-being of informal caregivers to patients before hematopoietic stem cell transplantation.</p> Method <p>A systematic review was conducted and analyzed in two subsets: one qualitative and one quantitative. (PROSPERO ID: CRD42023410710; 03/04/2022). An electronic literature search of PubMed, EMBASE, Medline, CINAHL, and PsycINFO was conducted up to July 2024. Full-text review and quality appraisal were completed independently and in duplicate by two reviewers with conflicts resolved by a third reviewer. Qualitative and quantitative data were tabulated together using thematic synthesis and then categorized according to outcomes of interest.</p> Results <p>Nineteen quantitative studies, two qualitative, and two mixed studies were included. Informal caregivers experience high levels of anxiety and depression before transplantation, facing varying degrees of psychological distress, stress, post-traumatic stress disorder, negative perceptions of transplant expectations, and moderate to severe caregiving burden. Qualitative research has identified two key themes: the empowering effect of information and the emotional burden of uncertainty.</p> Conclusion <p>Caregivers endure considerable emotional strain, caregiving burden, and unmet needs during the pre-transplant period. Medical staff must attend to the mental health and specific needs of informal caregivers before transplantation. Integrating informal caregivers into cancer care is essential to enhance the quality of nursing and, consequently, to optimize patient outcomes.</p>