Many people are affected by noise coming from traffic, industrial and construction activities or the neighborhood, resulting in activity disturbance, social tensions and health problems such as sleep deprivation, damage to hearing and cardiovascular diseases. An important way of protecting people from noise is by ensuring a sufficient overall sound insulation of buildings and building units. However, achieving a sufficient sound insulation of buildings is a complex problem since multiple transmission paths are important, uncertainties can have a large effect, and acoustic performance requirements often conflict with structural and thermal requirements. Furthermore, accurate vibro-acoustic modelling across the entire building acoustics frequency range requires a huge computational effort. As a result, the acoustic development of building systems has been typically based on general design rules, insufficiently accurate prediction models and many experimental prototype tests. Such development is costly and time consuming, and leads to suboptimal designs. This project aimed to develop an efficient yet sufficiently accurate prediction framework for the acoustic design of building systems which takes all uncertainties into account and which opens the way for design optimization. Four fundamental breakthroughs have been realized. The first is a new approach to high-frequency subsystem modelling that overcomes the limitations of the statistical energy analysis paradigm and handles a high degree of geometric and material complexity. Second, a modelling framework for built-up systems has been developed that incorporates different component model types and that switches between them as the frequency increases. The third development consists of quantifying the combined effect of all uncertain parameters on the overall sound insulation performance in a logically consistent and computationally efficient way. Finally, a robust optimization approach that spans the entire building acoustics frequency range has been developed. Each development has been complemented by showcase applications in building acoustics, yet the fundamental nature of the developments makes that they can impact all disciplines where the study and/or control of mechanical wave propagation are important.