While the deformation and damage behavior of aluminum cylinder heads under complex thermal mechanical loading has been the subject of numerous studies in the past, cast iron cylinder heads have been in the focus of thermomechanical fatigue (TMF) only to a minor extent. In this paper, a feasible procedure is presented to set-up material models and estimate service life of cast iron cylinder heads under variable thermomechanical loading conditions by the use of CAE tools. In addition, the influence of thermal load and mechanical constraints on TMF life span is shown. A specimen model is used for parameter identification in material model set-up and a cylinder head model is used for correlation with cracking phenomena. Investigation of different thermomechanical load influences is conducted on the cylinder head model. The principal strain and energy based fatigue criteria are used in assessment of TMF lifetime for the cast iron family and material specific evaluation procedures are pointed out. The results highlight the importance of exact definitions of the boundary conditions and underline the sensitivity of TMF lifespan of cast iron cylinder heads with respect to the defined boundary conditions. Considering this sensitivity, an approach conforming to the engine development requirements is proposed. It is shown that both the crack location and fatigue lifetime are predicted with high accuracy.