The present literature review builds on the results of 50 research articles published from 2000 until 2016. All these studies have successfully accomplished various learning tasks in the domain of Science, Technology, Engineering, and Mathematics (STEM) education using three-dimensional (3-D) multi-user virtual worlds for Primary, Secondary and Higher education, in order to: (a) present an overview about the potential contribution of this technology in practice-based perspectives on knowledge and learning; (b) identify the theoretical underpinnings based on contemporary learning theories and pedagogical approaches that leverage content design characteristics, with the respect to the constructs of their instructional design methods; (c) suggest a synthesis of the relevant literature about how the utilization of 3-D multi-user virtual worlds have affected positively learning outcomes based on students' achievements; (d) concretize the educational potential and instructional affordances covering the pedagogical (socio-) cognitive, technological-operational and financial perspectives; and lastly (e) propose an instructional design workflow to contextualize pedagogical content design principles for the implementation of different learning scenarios in STEM courses. The overviewed articles ascertained that 3-D multi-user virtual worlds have many instructional and technological affordances as candidate learning platforms for different educational levels, influencing to a large extent students' attendance, knowledge transfer, skill acquisition, hands-on digital experience and positive attitudes in laboratory experimental exercises. This technology gives to users the opportunity to manage learning materials more effectively and efficiently during the teaching process. The vast majority of educational benefits and potential enhanced the degree of their engagement and participation, contributing positively to their achievements.