Background: Chemotherapy-related cognitive dysfunction, one of the most frequently reported symptoms in patients with cancer, has a negative impact on the daily lives of patients. No research has examined cognitive dysfunction and its potential predictors in adult patients with cancer receiving chemotherapy in Saudi Arabia. Purpose: The purpose of this study was to examine the socio-demographic, clinical, and psychological factors associated with cognitive dysfunction in adult patients with cancer receiving chemotherapy. Methods: A cross-sectional correlational study was carried out with a convenience sample of 100 adult patients with cancer receiving chemotherapy at a university teaching hospital in Saudi Arabia. The Montreal Cognitive Assessment, the Hospital Anxiety and Depression Scale, and socio-demographic and clinical surveys were completed by participants. Descriptive statistics and linear regression were used to analyze the data. Results: The data showed that the participants experienced moderate-to-severe cognitive dysfunction. Participants performed poorly in the divided attention and memory cognitive domains. Age, educational level, and depression factors were found to be significant predictors of cognitive dysfunction. Conclusions/Implications for Practice: Cognitive dysfunction is commonly seen in patients with cancer receiving chemotherapy. Chemotherapy, age, and psychological factors increase susceptibility to cognitive dysfunction in adult patients with cancer. Oncology nurses should be aware that patients with cancer may be extremely vulnerable to cognitive dysfunction. Furthermore, age and psychological factors must be considered when developing symptom management and supportive care intervention programs to reduce the incidence of negative cognitive outcomes in this population.