In recent years, the digitization of cultural heritage has been favored by significant advancements in specific technologies, such as photogrammetry and three-dimensional scanning. The digital representations of artifacts, paintings, books, and collections, as well as buildings or archaeological sites, has led to the transfer of cultural organizations to the digital space. On the other hand, the rapid development of immersive technologies and the Internet of Things is expected to decisively shape virtual cultural heritage in the coming years. However, this digital transition should expand its impact on most of the population. This article aims to cover the lack of structured methodology in the design and development of inclusive virtual spaces in cultural heritage. This research introduces a holistic framework that is mainly based on the disciplines of virtual museology. The proposed methodology takes into account the advancements in extended reality and the creative industry of computer games. The multisensory approach would lead to advanced immersive experiences, while the multilayered approach of cultural heritage content would enhance accessibility in inclusive virtual spaces. Moreover, this holistic framework could provide evidence from the virtual worlds that could be applied to real cultural heritage organizations.