Urbanization consist in a complex and deep human-driven environmental change that strongly impacts the ecology and evolution of living organisms, including pathogens, reservoir and vector species hence human health. Quantitative proxies of urban landscapes may be very useful to sum-up such a complexity and to guide fundamental and applied research as well as urban planning programs. Geographic Information Systems (GIS) provide landscape and uses metrics which can be investigated through multivariate analyses, thus providing pertinent synthetic landscape descriptors. As such, our study describes the fine-scale modelling of three urban neighborhoods of Cotonou city, Benin, using GIS, landscape metrics and Principal Component Analysis (PCA). Spatial variability between and within neighborhoods revealed different levels of variability, with elements differentiating the three areas from each other, while local neighbourhood-specific variations were also evidenced. We found that Cotonou landscapes are strongly influenced by their history, the natural environment in which they develop as well as the urban planning trajectories. This case study shows that PCA-analyzed of GIS-based metrics may be very relevant to describe and understand the variability of urban landscapes at different scales, thus constituting a valuable tool for urban management of African cities.