Quality of Life (QOL) is an important outcome criterion in oncology and is a major concern of patients with cancer.However, most of them have been conducted in Western countries, and there are relatively few studies of this nature in Nigeria. It is in this light that this study examines the role of coping strategies, dispositional optimism, perceived social support and resilience on quality of life among cancer patients in Osogbo, Osun State. The Buffer theory of social support, stress and coping social support theory serve as the framework for the study. The study adopted a cross-sectional survey research design. A purposive sampling technique was used to select participants for the study.Data was collected using a structured questionnaire comprising socio-demographic characteristics, coping strategies, dispositional optimism, perceived social support, resilience and quality of life scales. Data was analyzed using zero-order correlation and hierarchical multiple regression analysis.The study found that coping strategies, dispositional optimism, and perceived social support predicts quality of life. The study also found that resilience moderated the relationship between coping strategies, dispositional optimism, perceived social support, and quality of life. The study concludes that coping strategies, dispositional optimism, and perceived social support are significant predictors of quality of life among cancer patients in Lautech Teaching Hospital, Osogbo, Osun State. Specifically, resilience was a significant moderator of quality of life among cancer patients as it acts as a buffer for cancer patients who have low social supports. The study suggests that quality of life can be improved by helping cancer patients to develop more supportive social networks, high level of optimism, stress coping strategy and building resilience may help in developing wellbeing in form of quality of life.