Urban systems are important consumers of resources and producers of wastes derived from the lifestyles and daily needs of their citizens. The quantification of environmental impacts arising from urban metabolism (UM) plays a key role in the design of more sustainable cities and in the development of decision-making strategies into more effective urban policies. This article combines UM and lifecycle assessment methodology to quantify mass and energy flows within the city limits and derived urban environmental pressures, thus prioritizing the environmental perspective of sustainability. This methodology is applied to the two very different Spanish cities of Bilbao and Seville. The results acquired in this study identify the consumption of construction materials, electricity, fossil fuels, and food and beverages as environmental hotspots. The results are primarily affected by differences in the climate (extreme conditions), which mainly affect the consumption of fossil fuels, and differences in purchasing power, which mainly influence the intake of foodstuffs. Further research should focus on data management and quality as well as on designing more efficient cities (e.g., through the introduction of more energy-efficient buildings, sustainable building materials, and public transport) in order to create improvements in their environmental profiles.