For a long time, there has been a need and an ambition to better understand the behavior of integrated systems by considering the whole urban water cycle, including wastewater transportation, wastewater treatment and the receiving water. On the other hand, fragmented environmental policies on wastewater sanitation, global change, and emerging contaminants are increasingly threatening freshwater ecosystems and human health. Within this context, this thesis embeds a series of research studies aiming to improve our comprehension of the functioning of urban wastewater systems (UWWS), considering both natural and artificial elements, and with a special emphasis on the occurrence of global change and on the fate of emerging contaminants. In the thesis, an integrated model for a UWWS in NE Iberian Peninsula has been developed and calibrated using data from an intensive and integrated survey, not only combining early developed mathematical models for the different sub-processes, but also verifying the model parameters with full-scale and dynamical measurements. More specifically, the work developed in this thesis was divided into three parts. First, we investigated how an UWWS perform together in the removal of conventional contaminants and evaluated the impact of future global change scenarios. Second, we investigated the occurrence and fate of pharmaceuticals and their transformation products in the UWWS. Finally, and as a continuation of the second work, we assessed the influence of the sampling strategy when estimating the loads and attenuation of emerging contaminants in UWWS under different scenarios differing from sampling strategies, consumption, and degradability of the compound under analysis. Overall, this thesis highlights the need for integrated approaches to better understand the performance of WWTPs and their receiving rivers, against the increase of micro-contaminants occurrence and the effects of global change.