Children, adolescents, and young adults with rare genetic syndromes, neurodevelopmental disorders, and multiple disabilities may experience significant problems while dealing with everyday life environmental requests. Besides extensive motor impairments, intellectual disabilities, and communication difficulties, they may exhibit challenging behaviors. Clinical conditions may be deleterious on their social image, status, and quality of life. A practical way to tackle this issue is represented by assistive technology-based interventions. A narrative review on the newest empirical contributions available in the literature over last five years (i.e., 2015-2020) was presented. Nineteen studies were reviewed. Five main categories of studies were identified, namely (1) adaptive responding, (2) executive functions, (3) communication, (4) gait and locomotion, and (5) challenging behaviors. Results were satisfactory although occasional failures were evidenced. Some helpful insights were emphasized, and future directions for both research and practice were critically discussed.