ABSTRACT Objective: To systematically analyze quantitative data about the effects of religion/spirituality and the well-being/quality of life of cancer patients. The second aim was to hypothesize a neurophysiological model of the association between religion/spirituality and the brain. Methods: This study met the PRISMA Statement and was registered at PROSPERO database. Randomized and Controlled trials investigating religion/spirituality and well-being/quality of life of cancer patients were included. Based on neuroimaging and neurophysiology studies, a neuroanatomical model was developed to hypothesize the relationship between neuroscience and religion/spirituality. Results: A large effect size was found on the improvement of well-being/quality of life (SMD = 3.90 [2.43-5.38], p < 0.01). Heterogeneity was high among studies (I2 = 98%, p < 0.01). Specific regions of the brain, such as the temporal lobes, amygdalae and hippocampus, regions from the limbic system, were hypothesized to take part in the religion/spirituality phenomena and the well-being/quality of life improvement. Conclusion: Religion/spirituality intervention, mainly the Islamic, promotes an improvement on well-being/quality of life of cancer patients.