In order to face increasing socio-economic challenges in a climate-change scenario, we should aim at re- designing our built environment, improving resilience and sustainability. Green infrastructure - trees in particular - play a critical role in urban heat island mitigation. Outdoor comfort simulations are useful tools to assess microclimate, and the different parameters influencing human energy balance and thermal comfort. The potential of bioclimatic design is illustrated testing the simulation tools Ecotect and City Sim on a dismissed iconic pharmaceutical factory in Rome (Italy), supporting its regenerative project, and thus offering useful insights for evidence-based design of urban post- industrial degraded sites.