Background: The Color Me Healthy symptom reporting app was co-designed with school-age children with cancer, their parents, and clinicians. Preliminary studies demonstrated its feasibility and acceptability; however, children and parents identified the need for additional refinements. Methods: Guided by the Technology Acceptance Model and principles of user-centered design, this study supported refinements to the Color Me Healthy user interface and evaluation of its usability. As the programming team completed builds of the app, school-age children with cancer and their parents participated in cognitive walkthrough usability evaluations and qualitative interviews. Usability logs documented the completion of key tasks related to reporting pain and review of child-reported data. Parents completed the Technology Acceptance Model Perceived Usefulness Scale (TAM-PUS). Interview responses were analyzed using qualitative content analysis. Results: Fourteen children (median age 8.5 years; range 6–12) and 14 parents (median age 38.5 years; range 34–49) participated in one of three usability evaluation cycles. After the third cycle, children and parents navigated the app and completed key tasks independently. Median TAM-PUS scores were 6 (range 6–8), indicating high perceived usefulness. Qualitative analyses indicated that children regarded the app as easy and fun to use. Parents emphasized the app’s developmental relevance for their child and for themselves as the child’s caregiver. Conclusions: This study demonstrates the perceived usefulness and perceived ease of use of the revised Color Me Healthy app. Optimizing the usability of the Color Me Healthy app with attention to the user needs of children and parents positions the app for wider-scale clinical implementation.