Urban populations in Asia, Africa, and Latin America are confronted with significant difficulties in accessing water due to inadequate infrastructure, limited governance capabilities, and the exacerbating effects of climate change, which further exacerbate water scarcity. This article investigates the physiological, environmental, and economic hardships that arise from insufficient access to quality water and sanitation infrastructure in cities of the Global South. Available evidence suggests that more than two billion individuals living in urban areas do not have access to water sources that are appropriately maintained. This lack of access has led to the widespread occurrence of diarrhoea diseases, particularly in marginalized informal settlements. There is a cumulative impact on households, municipal authorities, and national budgets due to economic losses resulting from healthcare expenses, decreased productivity, and limitations in the industrial sector. Reports also demonstrate severe water shortages caused by distinct local circumstances while also highlighting shared challenges of contamination, intermittent supply, and affordability problems that worsen inequality. While there are promising decentralized options available, as well as water efficiency and reuse advancements, there are still significant gaps in financing. It is estimated that an annual amount of $114 billion is needed to ensure access to safe water and sanitation for the increasing urban populations in the developing nations. Effective collaboration on a global scale and local administrative changes are crucial for addressing these deficiencies in infrastructure and enhancing the ability of mega cities in the Global South to withstand the escalating hazards posed by climate change.