Welds are metallurgically complex, with heterogeneous structures within the weld metal and heat-affected zones. In order to carry out a structural integrity assessment, it is important to have knowledge of the initial metallurgical features and the associated material property variations so that it is possible to accurately model all the possible failure modes of welds using, for example, numerical techniques. This paper describes some fundamental issues concerning a holistic process for high temperature performance and failure prediction assessment of power plant welds. This includes welding process simulation and residual stress determination, microstructural evolution and the formulation of creep damage mechanics constitutive equations including weld metal anisotropy. Typical examples, from specific case studies for P91 welds, are used to illustrate the application. Future requirements for development of high temperature assessment methods for welds are suggested.