Urban environments consist of a mosaic of natural fragments, planned and unintentional habitats hosting both introduced and spontaneous species. The latter group exploits abandoned and degraded urban niches which, in the case of plants, form what is called the third landscape. In the Anthropocene, cities, open spaces and buildings must be planned and designed considering not only human needs but also those of other living organisms. The scientific approach of habitat sharing is defined as reconciliation ecology, whilst the action of implementing the ecosystem services and functioning of such anthropogenic habitats is called Urban Rehabilitation. However, urban development still represents the main cause of biodiversity loss worldwide. Yet, the approach of planners and landscape architects highly diverges from that of ecologists and scientists on how to perceive, define and design urban green and blue infrastructure. For instance, designers focus on the positive impact that nature (generally associated with indoor and outdoor greeneries) has on human well-being, often neglecting ecosystems’ health. Instead, considering the negative impact of any form of development and to achieve the no net loss Aichi’s objectives, conservationists apply mitigation hierarchy policies to avoid or reduce the impact and to offset biodiversity. The rationale of this review paper is to set the fundamentals for a multidisciplinary design framework tackling the issue of biodiversity loss in the urban environment by design for nature. The method focuses on the building/city/landscape scales and is enabled by emerging digital technologies, i.e., geographic information systems, building information modelling, ecological simulation and computational design.