Buildings are responsible for approximately 30−40% of energy consumption in Europe, and this is a fact. Along with this fact is also evident the existence of a defined and strict legislation framework regarding energy efficiency, decarbonization, sustainability, and renewable energy systems in building applications. Moreover, information and communication technologies, along with smart metering for efficient monitoring, has come to cooperate with a building’s systems (smart buildings) to aim for more advanced and efficient energy management. Furthermore, the well-being in buildings still remains a crucial issue, especially nowadays that health and air quality are top priority goals for occupants. Taking all the above into consideration, this paper aims to analyze ventilation technologies in relation to energy consumption and environmental impact assessment using the life cycle approach. Based on the review analysis of the existing ventilation technologies, the emphasis is given to parameters related to the efficient technical design of ventilation systems and their adequate maintenance under the defined guidelines and standards of mechanical ventilation operation. These criteria can be the answer to the complicated issue of energy efficiency along with indoor air quality targets. The ventilation systems are presented in cooperation with heating and cooling system operations and renewable energy system applications ensuring an energy upgrade and reduced greenhouse gas emissions. Finally, the mechanical ventilation is examined in a non-residential building in Greece. The system is compared with the conventional construction typology of the building and in cooperation with PVs installation in terms of the environmental impact assessment and energy efficiency. The methodology implemented for the environmental evaluation is the Life Cycle Analysis supported by OpenLca software.