Background Cancer patients suffer from variable degrees of distress. The distress thermometer (DT) is a valuable tool for screening those patients for distress. Few studies have addressed the utility of DT in screening cancer patients in Saudi Arabia. We aimed to measure the distress level of adult cancer patients utilizing the DT and identify the appropriate measures and interventions required to improve this population's well-being. Methods This cross-sectional study was carried out at the oncology center of King Saud University Medical City (KSUMC), Riyadh, Saudi Arabia. Enrollment criteria were Saudi adults (≥14 years old), with a diagnosis of cancer, who gave informed consent. They were screened for distress using the DT and its associated problem list (PL). A workflow for a psycho-oncology supportive program was suggested. Results Using DT at a cut-off score of ≥4, 22% of patients had significant distress. The most frequent problems reported were loss/change of physical activity, swelling/edema, change in eating, family health problems, and child care. The multivariable binary regression analysis showed that sadness, depression, worry/anxiety, fear, loss of interest, change in appearance, taking care of myself, swelling/edema, and memory/concentration problems were independent factors for significant distress in our cohort. The suggested workflow could effectively be implemented among cancer patients. Conclusion The current study's findings support previous reports concerning the utility of DT in screening cancer patients for distress. A considerable number of Saudi cancer patients suffered from significant distress, which was significantly related to the emotional, spiritual, social, and religious aspects of their problems. We suggested a workflow by which cancer centers can implement DT screening after developing a plan for timely distress evaluation, with further proper management and referrals accordingly. Additional studies are warranted., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Alghamdi et al.)