A systematic of literature was carried out on peer-reviewed journals published from 2000 to 2015 to help in determining the best strategy of evidence-based practice that can be applied in teaching literacy skills among students with multiple disabilities. A total of 12 studies were reviewed, some of which included science and mathematics skills alongside literacy skills. The articles were evaluated according to the methodological processes used in carrying out the studies. Generally, all the strategies were found to be evidence based practices, which can be used to teach students with multiple disabilities. The systematic instruction and self-directed learning emerged as the most popular peer teaching and technology. Due to lack of enough studies that majored specifically on the students who suffered from more than one type of disability, other forms of severe disabilities like autism and intellectual disability, which are considered under the umbrella of multiple disabilities, were included in the systematic review. Additionally, in the process of defining certain target responses to demonstrate learning, with discrete responses being common, the type of feedback and systematic prompting that was commonly used was time delay, while stimulus fading was the least used component. One-to-one instruction and massed trials were the most commonly used formats for teaching. Though this is not a proof that systematic instruction is the best strategy, it is a suggestion that it is applicable in several situations and preferred by many researchers. Other strategies have also equally given positive responses and are thus effective in teaching literacy among students with multiple disabilities.