A systematic review of the pediatric cancer literature was conducted to identify and summarize the variables that influence family-level psychosocial outcomes and to develop a conceptual framework based upon the Family Stress Model. PubMed, PsychInfo, Web of Science, and CINHAL databases were searched between 2008–2018 using PRISMA. Empirical studies in this review examined both uni- and bidirectional relationships between at least two members within the family (e.g., parent and child) or measured a component of family functioning (e.g., cohesion, adaptability). After screening 2815 records, 10 review studies and 52 empirical studies met the study criteria for inclusion. Variables related to family-level psychosocial outcomes were synthesized into five thematic categories: family, parent/caregiver, child with cancer, immediate and extended relationships, and socioeconomic. Potential mediating and moderating effects reported included family cohesion, family ritual, family environment, family functioning, and parenting stress and caregiver burden. Based on this review, a conceptual path model was developed to illustrate factors pertaining to pediatric cancer that may be applied to the Family Stress Model (FSM). This adaption of the FSM in pediatric cancer integrates the factors of economic stress and pediatric cancer on outcomes related to family functioning and child/sibling psychosocial functioning that are central to families dealing with cancer diagnoses and can be utilized to explicate the relative strength and influence of risk and protective factors.