The neuroanatomical substrates that underlie dyslexia-dyscalculia comorbidity have not yet been reliably identified. We developed a novel neuroeducational approach to bridge the corresponding concepts on learning disabilities in the neuropsychological and psychoeducational fields. First, we assessed the cognitive profiles of individuals with reading, mathematical and both disabilities. Second, we performed a systematic review of the neuroanatomical substrates of dyslexia and dyscalculia. Third, we mapped the cognitive profiles to their neuroanatomical substrates. The comorbid group exhibited reading deficits which are associated with atypical function at the left inferior frontal and left fusiform gyri; they also exhibited deficits in quantitative reasoning, associated with a atypical function of the bilateral intraparietal sulci. Further deficits related to verbal working memory and semantic memory were exclusive to the comorbid group. Impaired phonological, numerical, semantic, and working memory processes may be associated with atypical function of the left angular gyrus in both reading and mathematical disabilities.