According to the United Nations (2020), since the 1980s, the global overall rate of water use has grown by 1% per year, and it is projected that, by 2050, humanity’s water footprint could exceed 30% of current levels. This situation is in stark contrast to the path toward the Sustainable Development Goals, especially Goal 6, “clean water and sanitation”, which also influences Goal 14, “life below water”, and Goal 15, “life on land”. This is because the availability of water directly affects the food security and production capacity of each Country, and therefore its management is a crucial issue worthy of particular attention. Problems related to water security are particularly evident in the Mediterranean area, which is already facing high environmental challenges. It is an area severely affected by global warming; thus, it is one of the most vulnerable environments to climate change globally. It follows that the improper management of water resources could further worsen an already alarming situation. This research aims to study the main water-related challenges that Mediterranean Countries face, highlighting the significant problems that weaken each Country. In this regard, the indicators relating to Goal 6 were considered, to define each Country’s current state. However, for a correct understanding, the main problems these Countries face were researched through a critical review of the literature (Scopus, Google Scholar, Web of Science). In this way, we were able to underline the effects of human activities on the hydrosphere and the repercussions on various ecosystems, following the drivers-pressures-state-impact-response causal framework. The results suggest that there is still a long way for Mediterranean Countries to progress toward Agenda 2030, as they face problems related to chemical (nitrate, microplastics, heavy metals, pesticides, etc.) and biological (E. coli and other microorganisms) pollution, as well as saline aquifers, absent or obsolete infrastructures, and transboundary basins. Hence, this study aims to provide valuable tools for a better evaluation of water management in Mediterranean Countries.