Context: Advanced cancer is one of the most complicated conditions for both patients and their relatives. This study aimed at investigating the challenges of home parenteral nutrition (HPN) in patients with advanced cancer. Evidence Acquisition: In this study, all articles published in English from 2000 to 2022 on dietary support for HPN in patients with advanced cancer were collected from several databases, including Medline, Scopus, and Google Scholar, using related keywords such as “advanced cancer” and “home parenteral nutrition”. Results: The different issues of HPN were examined for different dimensions such as HPN during palliative care, deciding HPN, patients’ safety, supportive environment, and health literacy. Regarding ethical issues on HPN, 4 principles including charity, autonomy, harmlessness, and justice should be considered in patients with advanced cancer. Considering recent findings on the beneficial effects of nutrients in patients with advanced cancer, there may be a need to revise the guidelines related to parenteral nutrition support in these patients. Conclusions: Different challenges should be especially considered in adopting appropriate approaches in the field of HPN in patients with advanced cancer. More longitudinal studies in this field are needed.