Background: Knowledge of the structure and function of the human heart is fundamental to accurately understanding human physiology. As a complex biological system, naïve conceptions abound regarding cardiac anatomy and physiology for K-12 learners and medical students alike. Objective: Textbooks and lectures, as well models and simulations, have had limited success in aiding learners in constructing accurate and cohesive knowledge of the human heart. Three dimensional (3D) modelling, haptic-enabled (HE) feedback, and interactive virtual reality (VR) experiences aid tertiary learners, yet it is unknown if secondary learners benefit from learning with these technologies. Methods: An exploratory study examined secondary student knowledge of cardiac anatomy and physiology after participation in an interactive lesson on cardiac structure and function using a 3D, HE, VR technology system. Students from sixth grade (11-12 years old; n = 75) and ninth grade (14-15 years old; n = 76) completed a pre- and post-assessment on cardiac knowledge, anatomy, and physiology punctuated by technology-delivered instruction on the human heart. Results and Conclusions: Significant gains were found in knowledge from both groups in cardiac anatomy and blood circulation within the chambers of the heart; however, only ninth grade students demonstrated significant knowledge gains in pulmonary circulation. Takeaways: Results suggest that 3D HE VR technologies provide learners robust representations of and student-driven interactions with complex biological systems that are innovative instructionally for strong conceptual and systematic learning. This study offers insight on technology-assisted science visualizations for the promotion of knowledge acquisition and systems thinking of the human heart among secondary science students.