Museums increasingly recognize the need to address advances in digital culture which impact the expectations and needs of their audiences. Museum collections of real objects need to be presented both on their own premises and digitally online, especially as digital and social media becomes more and more influential in people’s everyday lives. From interdisciplinary perspectives across digital culture, art, and technology, we investigate these challenges magnified by advances in digital and computational media and culture, looking particularly at recent and relevant reports on changes in the ways museums interact with the public. We focus on human digital behavior, experience, and interaction in museums in the context of art, artists, and human engagement with art, using the observational perspectives of the authors as a basis for discussion. Our research shows that the COVID-19 pandemic has accelerated many of the changes driving museum transformation, about which this paper presents a landscape view of its characteristics and challenges. Our evidence shows that museums will need to be more prepared than ever to adapt to unabated technological advances set in the midst of cultural and social revolution, now intrinsic to the digital landscape in which museums are inevitably connected and participating across the global digital ecosystem where they inevitably find themselves entrenched, underscoring the central importance of an inclusive integrative museum model between physical and digital reality.