To provide an effective alternative to sedation during MRI examinations in pediatric cancer and NF1 patients, the aims of the present study were to (1) exploratively evaluate a behavioral MRI training program, to (2) investigate potential moderators, as well as to (3) assess the patients’ well-being over the course of the intervention. A total of n = 87 patients of the neuro-oncology unit (mean age: 6.83 years) underwent a two-step MRI preparation program, including training inside the scanner, and were recorded using a process-oriented screening. In addition to the retrospective analysis of all data, a subset of 17 patients were also analyzed prospectively. Overall, 80% of the children receiving MRI preparation underwent the MRI scan without sedation, making the success rate almost five times higher than that of a group of 18 children that opted out of the training program. Memory, attentional difficulties, and hyperactivity were significant neuropsychological moderators for successful scanning. The training was associated with favorable psychological well-being. These findings suggest that our MRI preparation could present an alternative to sedation of young patients undergoing MRI examinations as well as a promising tool for improving patients’ treatment-related well-being.