Nowadays, the implantation of cultural and creative industries into the historic blocks of inner cities is widely accepted. With controversial impacts on heritage, the sustainability of culture-led regeneration has got increased research attention. This study focuses on cultural impact of the regeneration, as the creation of identity is the core of these new industries and might be the internal source of sustainability. Originally, it considers historical heritage as a production and marketing resource, while the regeneration process may have a negative impact on the former local identity and image. Responding to this paradox, we emphasize that the evaluation of the cultural impact of the implantation of new industries into historic blocks must consider multicultural backgrounds, because the culture-led regeneration actually hybridizes the conservation of former local identity and expression of contemporary identity. It can be stimulated by multiculturalism and is realized through the work of cultural entrepreneur with enhanced mobility, transcultural experience, and cultural sensitivity. Therefore, the identity of these new entrepreneurs and their spatial preferences may directly influence the regeneration results. Thus, this study not only demonstrates the physical regeneration results but also explores the relation between physical transformation and complexity of cultural identity, through the case study of Wudaoying Hutong in Beijing, a regenerated historic block with multicultural imprints. First, space syntax was used to investigate spatial transformation. Next, a bilinear measurement model of acculturation was used through a combination of questionnaires and in-depth interviews, and the corresponding acculturation conditions of new entrepreneurs were observed. Finally, the correlation between the spatial results and the acculturation measurements was verified and the implicit dynamics between acculturation conditions and the regeneration strategy was interpreted.