Background & Aims: In the age of information and knowledge, the necessity of using virtual reality techniques for teaching nursing knowledge and skills, considering the sensitive tasks of nurses, is nothidden from anyone. Simulation-based educational software with high realism and quality are notable strategies to limit the risks of nursing education based on traditional method that can improve patient safety and reduce medical errors. The present study aimed at analyzing the role of models, approachesand learning theories in the design and production of educational software based on virtual reality techniques and simulation in nursing.Materials & Methods: For the purpose of the present systematic review, all articles which were published from 2000 to 2015, which were related to educational software based on virtual reality in nursing both in English and Farsi were analyzed. To search for the study, databases such as SID, CINAHL, PubMed, Web of Science, EBSCO Host, Irandoc, Iranmedex, Google Scholar and relevant journals were used by using key words including education, nursing, theories of learning, software, simulation-based, computer-based, virtual reality techniques, models and their combinations. Severalsteps were taken for selecting and analyzing the full text of these studies. And, the articles whichqualitatively met the inclusion criteria were assessed by using the relevant checklists.Results: Of the 850 articles that were related to the use of educational software based on virtual reality techniques and simulation in nursing, 12 articles which were directly related to the purpose of the study were chosen for further analysis. Of the 12 articles, four articles considered learning as a cognitive phenomenon. Five articles had used Jefferies simulation model and principles of learning theories.Conclusion: The study concludes that the educational centers for training skilled nurses need the educational software based on virtual reality techniques as an educational tool, it seems necessary todirect the purposes of simulators toward learning based on professional competence paradigm with theuse of simulation models and learning theories.