We conducted this systematic literature review to summarize single-case intervention studies in which academic instruction incorporated assistive and instructional technology for students with complex support needs. Thirty studies, published between 2012 and 2019, were included in the review and evaluated for methodological rigor. Of the 97 student participants across all studies, most received language arts instruction in self-contained elementary classrooms. The majority of interventions used instructional technology on mobile devices in conjunction with systematic instruction focusing on teaching word recognition or letter identification skills. We discuss the key findings with recommendations for future research, and implications for practice.