One of the most pressing needs to advance childhood cancer research is a comprehensive, modern infrastructure for storing, integrating and sharing all data types collected longitudinally from cancer patients, especially for the integration of patient-reported outcomes (PROs) with clinical, environmental and genomic data. While there are efforts to amass large multiomic datasets, such as the St. Jude Cloud and Treehouse Childhood Cancer Initiative, we should not neglect the critical need for longitudinal clinical and PROs assembled into a standardized analysis framework interconnected with genomics. While The Cancer Genome Atlas project provided unprecedented insight into the molecular profiles of adult cancers, its continued impact has been limited by lack of longitudinal, in-depth clinical outcomes. As the childhood cancer survival rate continues to increase, patient-derived data is critical to understand the significance of physical activity, nutrition, and environmental factors on short- and long-term outcomes, including susceptibility to late effects as a result of treatment. To enable longitudinal data collection, researchers should leverage modern technology, such as non-invasive wearable devices and mobile apps, to collect physical activity, patient-reported symptoms, medication adherence and so forth. Collecting PROs in adult cancer patients has been shown to increase overall survival and similar results are expected in pediatric patients to predict, detect and treat adverse events or late effects earlier. As researchers collect PROs from wearable and mobile platforms the vital need will quickly become the cohesive integration of these data with other data, such as electronic medical records and genomics. Therefore, we propose that an innovative data infrastructure that can harmonize longitudinal data from all sources will be an essential element to advance childhood cancer research.