This systematic review of qualitative studies was conducted to identify the factors that influence how pre-service science/math teachers implement the 5E instructional model and the challenges and barriers they face in doing so. Sixteen studies were identified in various electronic databases, and a meta-ethnography method was used to review the qualitative studies. The findings illustrate that the experiences of the pre-service teacher varied. Time, resources, method courses, training, field experience, beliefs, content knowledge, and classroom size were identified as influences on the practice of pre-service teachers. To sum up, this review provides a better understanding of pre-service teacher experiences in implementing the 5E instructional model.