Phytoremediation can be a promising and sustainable strategy to recovery Potentially Toxic Elements (PTEs) contaminated soils. However, at the field level, this tool can be limited by many issues. Herein, we combined native plant species with different cover type (mono and poly culture) in an in-field mesocosm experiment for the remediation of multi-contaminated soils from Bagnoli brownfield site (Southern Italy). We preliminary gain insights about the physical, chemical and biological features of the soils and subsequently induced a potential variation in the soil microbiome. We found that polyculture better respond both in terms of pollutant phytostabilization efficiency and from a stress tolerance perspective. Among plant species, Festuca achieved the best performance due to the overexpression of metal transporters able in both PTEs influx and sequestration from the cytoplasm. We achieved a site-specific bio-factory, which represents a strategy for the sustainable and relatively fast recovery of large contaminated areas.