As twenty-first century skills become a greater focus in K-12 education, an infusion of technology that meets the needs of today's students is paramount. This study looks at the design and creation of a Multiplayer Educational Gaming Application (MEGA) for high school biology students. The quasi-experimental, qualitative design assessed the twenty-first century skills of digital age literacy, inventive thinking, high productivity, and effective communication techniques of the students exposed to a MEGA. Three factors, as they pertained to these skills, emerged from classroom observations. Interaction with the teacher, discussion with peers, and engagement/time-on-task while playing the MEGA suggested that students playing an educational video game exhibited all of the projected twenty-first century skills while being engrossed in the embedded science content. (Contains 2 figures.)