Decarbonization: Achieving the decarbonization of the European building stock by 2050 requires deep energy renovation of buildings and neighbourhoods without compromising indoor health. We need to improve our design approach to reduce the carbon footprint of our buildings to achieve the new aim of Zero Emission Buildings (ZEB). Health: As we spend more time indoors, we expose ourselves to multiple pollutant sources and microbes. The COVID-19 pandemic has revealed our lack of knowledge about the transmission of respiratory diseases in buildings. Conscious buildings: Increasing digitization opens new opportunities to optimize the design, operation, and indoor environmental quality (IEQ) of new or refurbished nearly zero-energy buildings (NZEBs). However, technically advanced sensor-based measurement and control (e.g., demand-controlled ventilation) pose numerous challenges. Future climate data: The climate is changing, and we need to consider its impact on building design and operation. For instance, will more cooling or heating capacity be needed? What energy conservation technologies will be most effective in the future? At present, there are no standardized methods for estimating future climate impacts on building systems.