As we enter a world of blended learning in higher education, an increased need for adaptation of teaching strategies to enhance engagement has been recognised to amplify learning outcomes online. Gamification has been identified as a creative tool to engage the current cohort of learners who are also characteristically tech-savvy. To this end, escape room games have gained considerable traction in medical and pharmacy education to promote learning, critical thinking and teamwork. In this pilot study we describe the implementation of a 60-minute, web-based hepatitis-themed escape room game within a Year 3 Pharmacotherapy unit at Monash University. A total of 418 students participated in this activity. Students' knowledge gain on the topic was assessed through a pre- and post-intervention assessment, whereby a statistically significant improvement was seen in the knowledge score following implementation of the gaming activity (58.66% pre-intervention vs. 72.05% post-intervention, p < 0.05). The innovative learning activity was also well perceived by the students. Virtual escape room game is a viable pedagogical approach to teach and reinforce clinical concepts among pharmacy students. With the evolving landscape of education and learner demographics, investment in technology- enhanced game-based learning is a promising trajectory to support students' growth in a learner-centered environment. A comparison between virtual escape room game and traditional teaching will further inform effectiveness of the gamification on long term knowledge retention.