Purpose: The rate of incidence of childhood cancer has increased by 0.6% per year since 1975 with an estimated 10,590 children between the ages of 0 and 14 years to be diagnosed in 2018 (Siegel, Miller, & Jemal, 2018). Amidst diagnoses and treatment plans, spiritualty is often overlooked among this population; however, assessing spirituality at diagnosis and during care can impact quality of life (Kamper, Van Cleave, & Savedra, 2010). When considering spirituality in pediatric oncology patients, a neurobiological model provides a more comprehensive perspective of these children and adolescents. By better understanding the spiritual needs of patients in relation to brain function, we, as providers, can provide better supportive care to pediatric oncology patients to make sense of their diagnosis and developing worldview. Methods: We reviewed the literature concerning: the development of spirituality in healthy children, how the development of spirituality changes in children with cancer, the neurological development of healthy children, and how cancer and cancer treatments affect neurological development in pediatric oncology patients. We then created a combined neurological-spiritual model to guide the caring of pediatric oncology patients. Results: As most children mature neurologically, the volume of white matter increases while gray matter decreases (Toga, Thompson, & Sowell, 2006; Lebel & Beaulieu, 2011). This neurological development can be hindered by chemotherapy treatments as certain chemotherapies can result in white matter abnormalities and decreases in white matter volume (Wilson et al., 1991; Qiu, et. al., 2007; Chu et. al., 2003). White matter development is imperative for healthy brain maturation and to draw cognitive connections (Hagmann, et. al., 2010) and since neurological development affects spiritual development (Urgesi, et. al., 2010; Newberg, 2014; Newberg, et. al., 2010), this change in white matter development can have consequences on a child’s spiritual development. Fowler indicates in his spiritual development trajectory that children often view the world concretely and over time will develop abstract perspectives and thought (Fowler, 1981). However, if this spiritual trajectory is predicated on neurological development which can be altered with chemotherapy, pediatric oncology patients may then develop an altered spiritual development as well that coincides with white matter changes. Although the literature on spirituality in pediatric oncology patients has varied findings, there are studies that support this hypothesis (Hendricks-Ferguson, 2008; Kamper, Van Cleve, & Savedra, 2010). Future directions of our research include investigating our model through analysis of fMRI imaging of pediatric oncology patients and creating interventions to boost white matter development during chemotherapy treatments. Conclusion: By drawing connections between science, spirituality, and medicine, we can better serve the needs of our patients’ ability to cope with illness, optimize the spiritual self, mitigate emotional, cognitive, and physical symptoms, and hopefully improve treatment outcomes.