Science, technology, engineering, and mathematics (STEM) is a meta-discipline employing active, problem-centric approaches such as game-based learning. STEM competencies are an essential part of the educational response to the transformations caused by the fourth industrial revolution, spearheaded by the convergence of multiple exponential technologies. Teachers’ attitude is a critical success factor for any technology-enhanced learning innovation. This study explored in-service teachers’ views on the use of a digital educational escape room in virtual reality. Forty-one (n = 41) K-12 educators participated in a mixed research study involving a validated survey questionnaire instrument and an online debriefing session in the context of a teacher training program. The key findings revealed that such alternative instructional solutions can potentially enhance the cognitive benefits and learning outcomes, but further highlighted the shortcomings that instructional designers should consider while integrating them in contexts different than the intended. In line with this effort, more systematic professional development actions are recommended to encourage the development of additional teacher-led interventions.