Background: Interactive engagement, specifically attention and initiation, are considered important skills for facilitating development and learning in students with severe/profound intellectual and multiple disabilities. Prior research has suggested that music therapy and multisensory storytelling are two promising interventions for supporting interactive engagement in this population. However, there are no known/published studies that have investigated the effect of combining relevant elements from musical interaction and multisensory storytelling for this group of students. This study aims to determine the effect of a novel educational approach--MultiSensory Music Drama (MSMD)--on the interactive engagement of students with severe/profound intellectual and multiple disabilities. Methods: A single-case experimental design, specifically an ABAB design across three participants, was used to describe the effect of MSMD on interactive engagement when compared with a control activity. School staff members' perceptions of student interactive engagement and social validity were obtained. Findings: Coded video observations showed significantly higher levels of interactive engagement during MSMD for all three participants when compared to the control activity. Furthermore, the ratings on the interactive engagement from school staff members improved for two of the three participants. Finally, school staff members scored the social validity and perceived educational usefulness of the MSMD as very high. Conclusions: The findings provide initial evidence that MSMD may be effective in supporting the interactive engagement of some students with severe/profound intellectual and multiple disabilities.