Rapid population growth coupled with metropolitan activities globally intensifies greenhouse gas (GHG) emissions, mainly carbon dioxide (CO2). Increased energy consumption and carbon emissions, changes in precipitation and humidity, and severe weather conditions are just a few of the impacts of climate change (CC). In addition, energy costs have been rising steadily because of the global economic crisis that impacted steady supply, which has an impact on the prices of daily goods. Moreover, the intensified urban heat islands effect (UHIE), due to recent heat waves that hit Europe and South Mediterranean cities between July and August 2023, prompts the need for immediate actions to encounter such unprecedented and sweltering heat caused by high air temperatures reaching 43 °C, 44 °C, and 46 °C in Cairo, Egypt, Rome, Italy, and Madrid, Spain, respectively. In the endeavour to mitigate CC, experts and scholars have diligently explored various strategies to create zero-carbon cities (ZCCs) by improving urban and regional landscapes to sequester carbon from the atmosphere. Among these strategies, vertical farming (VF) has emerged as a pioneering innovation in urban agriculture in cities, leading to the application of workable and generative solutions in the construction of interactive urban areas that perform productive functions while also being required to enhance the city’s liveability, improve residents’ health and well-being, and attain the sustainable development goals (SGDs) and achieve carbon neutrality. Vertical farms are also thought to be an alternative to resource depletion because they generate large amounts of fresh and clean agricultural products while also utilizing less water. This can generally withstand weather fluctuations and act as an element of green infrastructure to mitigate flood impacts and improve cities’ resilience. The study aims to delve into how VF can be used as a tool to mitigate CO2 in urban areas and cities. It also examines the potential of VF to achieve a zero-carbon strategy (ZCS) in urban areas, particularly in hot-arid climates, which face land scarcity and high land values. The methodology encompasses two approaches: first, a theoretical approach, and second, an applied approach that is based on a comparative life cycle assessment (LCA) for VF. The study analyses a system of vertical hydroponic farms in a residential building in New Cairo, Egypt, and compares their environmental and economic implications to conventional rural agriculture in terms of water efficiency, land use, and CO2 emissions using the LCA methodology. The results demonstrate that VF in hot-arid cities such as New Cairo can significantly reduce GHG emissions and water consumption while producing large volumes of fresh agricultural products. The results also substantiated by a comparative financial analysis between hydroponic and traditional cultivation systems provide robust support for the viability of VF from a triple bottom line perspective. Consequently, this study highlights the pivotal role of establishing efficient VF systems as a cornerstone towards realizing a ZCS in urban areas and thereby promoting efforts towards climate neutrality.