South Africa’s urban population is increasing, and in parallel, urban green infrastructure has shown an increase in alien tree species, e.g., mulberry (Morus sp.), oak (Quercus spp.) and plane trees (Platanus spp.) to name a few. This causes ecological problems since alien trees are often more water-demanding and competitive than indigenous trees, but they also increase the abundance of respiratory diseases often triggered by an allergic reaction towards the pollen of those alien taxa. In the current study, utilizing 7-day volumetric spore traps, we illustrate that the most abundant tree pollen in the two largest cities of South Africa, Cape Town and Johannesburg, is produced by alien trees with a high risk of allergenicity. This adds another aspect related to public health when evaluating plant species composition in urban forestry and urban ecology, which underlines the urgency of more intense monitoring. More importantly, this—for South Africa—newly emphasized risk for public health underlines the applicability of current directives [i.e., Spatial Development Frameworks (SDFs), localized Precinct Plans, Land Use Schemes (LUSs)] and implementation options in urban planning. Here, we present ideas that may be implemented in such a framework. From both a public health and an ecological perspective, it is recommended to plant indigenous trees like Combretum erythrophyllum, Vachellia and Senegalia spp. that have fewer ecosystem disservices, like a lower impact on public health due to lower allergenicity/lower pollen occurrence and providing more ecosystem services such as lower water needs.