Cancer-related fatigue is a common and distressing cancer symptom that negatively affects quality of life. The main objective of this study was to determine health professionals' knowledge relating to cancer patients' fatigue in Oman and identify current management practices of cancer-related fatigue. A cross-sectional survey design using Qualtrics® software was performed. The survey had five sections and comprised 32 items. A total of 138 healthcare professionals working in Oman participated in the study (response rate 63.9%). Nearly three quarters of the participants were nurses (74.6%, n = 103). The mean level of knowledge of cancer-related fatigue was 16.6/23, with 50% of participants having the expected level of knowledge above 12. The result indicated that professional discipline and work experience each were significantly associated with overall level of knowledge. Participants identified the need for guidelines, assessment tools, and training for the oncology staff to help improve the quality of life of patients with cancer-related fatigue.