Energy efficiency measures in residential buildings typically include changes in ventilation and heating systems, and increased thermal insulation of the building envelope. The expected energy efficiency is not always reached, despite large knowledge and professional implementation of each separate measure. There is a lack in understanding of how technical systems interact, and how the occupants are influenced by and in turn influence the systems by their behaviour. A holistic view and a transdisciplinary research approach are needed to understand relevant interactions and propose integrated energy efficiency measures. The aim of this paper is to reveal challenges in transdisciplinary research projects that include real world studies on both humans and technical systems with measurements before and after renovation of multifamily housing. It is based on experiences from the PEIRE-project (People, Environment, Indoor, Renovation, Energy) carried out by a research team with expertise on environmental psychology, human behaviour, interaction design, universal design, building physics, building services, thermal comfort, aerosol technology, exposure assessment, acoustics, daylight, and complex thinking. Differences in theoretical bases and methodology needed to be dealt with. Metatheory building could help with the transition from a multi- to a transdisciplinary understanding.