The urbanization process, which began with the Industrial Revolution, has undergone a considerable increase over the past few decades. Urbanization strongly affects ecological processes, often deleteriously, because it is associated with a decrease in green spaces (areas of land covered by vegetation), loss of natural habitats, increased rates of species extinction, a greater prevalence of invasive and exotic species, and anthropogenic pollutant accumulation. In urban environments, green spaces play a key role by providing many ecological benefits and contributing to human psychophysical well-being. It is known that interactions between plants and microorganisms that occur in the rhizosphere are of paramount importance for plant health, soil fertility, and the correct functioning of plant ecosystems. The growing diffusion of DNA sequencing technologies and “omics” analyses has provided increasing information about the composition, structure, and function of the rhizomicrobiota. However, despite the considerable amount of data on rhizosphere communities and their interactions with plants in natural/rural contexts, current knowledge on microbial communities associated with plant roots in urban soils is still very scarce. The present review discusses both plant–microbe dynamics and factors that drive the composition of the rhizomicrobiota in poorly investigated urban settings and the potential use of beneficial microbes as an innovative biological tool to face the challenges that anthropized environments and climate change impose. Unravelling urban biodiversity will contribute to green space management, preservation, and development and, ultimately, to public health and safety.