Attention-deficit/hyperactivity disorder is one of the most common comorbidities in individuals with autism spectrum disorder. However, the clinical implications of the co-occurrence of these two disorders are still poorly understood. Based on a preregistered protocol (PROSPERO CRD42020193880), this systematic review identified 34 articles, published between January 1, 2014, and September 1, 2020, on cognitive, adaptive/social, and behavioral manifestations in children and adolescents with a diagnosis of autism spectrum disorder and attention-deficit/hyperactivity disorder (ASD+). The majority of available studies found a tendency toward a significant poorer cognitive performance in individuals with ASD+ compared with those with autism spectrum disorder alone (ASD-). The analysis of social/adaptive processes suggested that ASD+ is associated with lower functioning in comparison with ASD-. Finally, individuals with ASD+ were more likely to develop emotional/behavioral difficulties, in particular externalizing problems. Although some studies did not find differences among the two groups, overall co-occurring ASD+ may constitute a distinctive phenotype with a greater likelihood of cognitive, adaptive dysfunction, and mental health symptoms compared with ASD-. These results may inform the setting up and implementation of care pathways for individuals with attention-deficit/hyperactivity disorder and autism spectrum disorder.