Background: Parent-mediated intervention (PMI) is a potentially scalable approach for tailored interventions in neurogenetic conditions like Down syndrome (DS). Because PMIs require ongoing parent engagement, they must be developed in alignment with the needs of intended users. The present study examined caregiver opinions and preferences to inform the development of syndrome-informed interventions for children with DS. Method: Parents of children with DS (n = 34) participated in focus groups discussing PMI. Interviews were transcribed and a thematic analysis was applied to code the data. Results: Three themes were identified: advantages of PMI, disadvantages of PMI and preferred features of PMI. To align with parent preferences, future PMIs for children with DS should require a brief time commitment, blend intervention activities into daily routines and include family members in activities. Conclusions: Findings have implications for developing novel interventions to support early development in children with DS and other neurogenetic conditions.