Hydrological processes and water resources are increasingly modified by anthropogenic actions, leading to multiple pressures on the environment and related ecosystems. A better understanding of the interactions between the anthroposphere and the hydrosphere is necessary to shape more sustainable societies. The pressure of human activities on the environment is especially high along the circum-Mediterranean area because of a combination of biophysical and economic factors. The Campo de Cartagena coastal plain, together with the Mar Menor lagoon, is one of the most exemplary areas in this aspect. This work analyzes this system at the basin level by providing a synthesis of the state of knowledge of each hydrological compartment and the links between them. We pay special attention to the important role that groundwater plays in the overall functioning of the system, both as a promoting and (or) mitigating agent. The principal identified impacts from human actions are water imbalance (28% of consumed water resources are not renewable); aquifer-cross contamination (high areal density, similar to 1.2 wells/km(2)); acid-mine drainage (mine wastes, accounting for similar to 175 hm(3) on land and similar to 25 hm(3) in the sea, accumulated mainly between 1957 and 1992); and lagoon eutrophication (NO3- up to 1 mg/L). A set of mitigation options and complementary management measures that should be implemented following an integrative and holistic approach are presented and discussed, supporting a more sustainable regional economy and the recovery of critical ecosystem services.