Demoralization can be understood as a condition that results from existential conflict. It presents with symptoms of hopelessness and helplessness caused by a loss of purpose and meaning in life. It is a significant mental health concern given there can be an associated desire for hastened death. OBJECTIVES: The aim of this systematic review was to synthesize the recent empirical evidence on demoralization in patients with progressive disease or cancer, including prevalence rates; the relationships between demoralization and sociodemographic, disease- and treatment-related, and psychological factors; as well as the psychometric properties of demoralization measures. METHODS: A comprehensive literature search using key words and subject headings was performed following PRISMA guidelines with nine electronic bibliographic databases, resulting in 25 studies (33 papers) with a total of 4545 participants reviewed. Full papers underwent methodological quality assessment and correlational information was synthesized according to the strength of evidence. RESULTS: The findings suggest that demoralization is prevalent in patients with progressive disease or cancer and clinically significant in 13-18 . A range of factors were consistently associated with demoralization: poorly controlled physical symptoms, inadequately treated depression and anxiety, reduced social functioning, unemployment, and single status. The Demoralization Scale (DS) has demonstrated good psychometric properties across five studies. CONCLUSION: Overall, this systematic review was limited by the extent of variability in the characteristics of studies. Patients who are single, isolated or jobless, have poorly controlled physical symptoms, or have inadequately treated anxiety and depressive disorders are at increased risk for demoralization. Clinical recognition of demoralization can trigger more focused interventions.