A 2200 cc engine head for marine applications has been analysed and optimized by means of both fluid-dynamic and thermo-structural simulations. First, the fluid distribution within the cooling jacket has been deeply investigated, in order to point out critical aspects of the current jacket layout and propose modified gaskets aiming at modifying the coolant path and increasing the cooling performance. A new generation polyhedral grid has been employed to combine high resolution surface spacing, computational demand, and numerical stability of the CFD simulations. Different turbulence models and near-wall approaches have been tested in order to accurately predict the boundary layer behaviour, which is fundamental for the subsequent thermal analysis. Comparisons have been carried out between the different gasket layouts in terms of both cylinder to cylinder flow balancing and cooling effectiveness in the critical regions of the engine head. At a second stage, the CFD model has been extended to the whole engine head, i.e. covering both the cooling jacket and the metal cast, and heat flux distribution on the fluid/solid interface has been computed and transferred as a boundary condition to a structural finite elements code for the analysis of the fatigue strength of the component. To this aim, an ad-hoc developed routine has been created to map the computed punctual distribution of the heat transfer coefficient on a FEM-optimized grid. Particular attention has been paid to the thermal boundary conditions, i.e. the distribution of the heat losses among the combustion chamber and pre-chamber components. Along with this coherent approach of thermo-mechanical loading, the mechanical constitutive law of the material, the damage parameters and an energy based fatigue strength criterion have been considered in order to create a design strategy capable of performing predictive calculations of automotive parts subjected to thermo-mechanical loading. The methodology favoured in this study has been successfully applied to predict the site of incipient crack on an actual engine head.