Process evaluations provide insight into the implementation of complex interventions. This study is a process evaluation for the implementation of a parent-led physical activity intervention at home with youth with a rare neurodevelopmental disorder (Prader-Willi syndrome, PWS) and youth with non-syndromal obesity (NSO). Participants included 42 youth with PWS (10.9 ± 2.5 y; 24M: 18F) and 65 youth with NSO (9.8 ± 1.1 y; 34M: 31F), assigned to an intervention or a delayed intervention group. The 24-week intervention included parent training, receiving equipment and a pre-planned curriculum with playground games and interactive console-based games. We evaluated intervention implementation fidelity, dose (reported physical activity minutes), acceptability (perceived difficulty and enjoyment of the planned activities) and contextual factors (facilitators and barriers). Overall, 68.2% of participants (immediate and delayed intervention groups) completed = 70% of the planned physical activity sessions. The average length of the sessions was 44 ± 23 and = 49 ± 22 min for playground and console-based games, respectively. Most activities were more difficult for those with PWS than those with NSO. Common barriers to implementation included scheduling and the child's motivation, and facilitators included features of the curriculum and social support. This intervention modality (home-based, delivered by parents) appears suitable for families with children with and without neurodevelopmental disorders.