The turbine housing of a turbocharger is exposed to extensive cyclic thermo-mechanical loading. This leads to multiaxial stress states with local plastifications, so that the design of the turbine housing becomes a major challenge in ensuring the guaranteed lifetime in relation to the high-temperature behavior of the materials. In a first step, a phenomenological lifetime approach in conjunction with a constitutive material model applied in a preceding finite-element analysis was developed and validated for application on the casting materials Ni-resist D5S and vermicular cast iron GJV. The present study deals with the adaption for turbine housing design together with the more detailed analysis of application-specific phenomena to improve the description of both the deformation behavior and the creep-fatigue damage behavior. The influence of different strain rates, mean strain conditions, and aging has been evaluated. Moreover, a critical plane approach has been investigated to handle multiaxial stress and strain states. A more accurate damage ratio is derived by use of specimens subjected to characteristic thermo-mechanical load conditions, which leads to an improved estimation of the cycle number until crack initiation on critical component positions.