Background: Cachexia is a syndrome of muscle wasting, weight loss, and anorexia, that frequently affects patients with advanced cancer across all major areas of oncology (surgical, medical, radiation, and chemotherapy), contributing to poorer treatment outcomes, including survival. In this qualitative systematic literature review, we reviewed the recent literature to assess the impact of cancer cachexia on chemotherapy dose reduction, treatment discontinuation, and survival. Methods: A systematic search was conducted on PubMed and Embase on November 26th, 2021, using the following search terms, among others: “cancer”, “cachexia”, “sarcopenia”, “muscle loss”, “body weight loss”, “chemotherapy”, “drug dose reduction”, “survival”, “treatment withdrawal”, and “treatment interruption”. 1,559 entries published between 2018 and 2021 were identified, of which 175 were duplicates. Publications were screened for eligibility and only original research in peer-reviewed journals were considered eligible. Inclusion criteria included: chemotherapy-specific studies; studies reporting on cachexia, body weight, or body composition changes; and studies reporting data on survival, chemotherapy dose reduction or treatment discontinuation, or occurrence of toxicities which may lead to chemotherapy dose reduction or treatment discontinuation in these patients. All studies that did not analyze the impact of cachexia on these outcomes were excluded. Results: A total of 63 studies, comprising a total of 15,832 patients, were considered eligible and selected for further analysis. The majority of analyzed studies, comprising 14,493 patients, reported associations between cancer cachexia (or its characteristics, such as weight loss or muscle wasting) and chemotherapy dose reductions in 7% of the studies, treatment discontinuation in 20% of the studies, and increased toxicity in 25% of the reports. Cachexia parameters were associated with inferior survival in 90% of the studies. The types of cancer most commonly associated with this effect were pancreatic (31% of studies), foregut (gastric, esophageal, and others, 17%), and lung cancer (14%). Conclusions: More than 70% of studies identified in the literature were retrospective assessments of patient records, while the remaining were prospective observational and interventional studies. In this review, cancer cachexia parameters were associated with reduced treatment delivery and inferior survival in multiple types of advanced cancer. These observations could have important implications for clinical practice, as early detection and successful treatment of cachexia might provide better outcomes for cancer patients undergoing chemotherapy. Disclosure: This study was funded by Helsinn Healthcare SA. Contact: Gianluca.Ballinari@helsinn.com.