We argue that current cultural developments, driven by innovative technology, call for a reconsideration of the role of humanities as a field of study in which art and science is tightly integrated. This integration would allow the humanities to develop a proactive power such that it can (co-)steer the innovative developments of the techno-culture. Integrated art-science research may be realized in contexts where human expressive interaction with multimedia is investigated. Research outcomes from this domain may offer opportunities for humanities to contribute to cultural developments. Given the context of interactive multimedia, we offer a theoretical framework based on art-science research concerning: (1) human interaction, (2) interaction systems, and (3) cultural and societal interaction outcomes. The goal of the framework is to contribute to a new ambition for the humanities, one in which knowledge about culture, on top of being reflective, critical, and descriptive, has an intrinsic power to contribute to innovative techno-cultural developments.