Fast and high-fidelity combustion models including detailed kinetics and turbulence chemistry interaction are necessary to support design and development of heavy-duty diesel engines. In this work, the authors intend to present and validate tabulated flamelet progress variable model based on tabulation of laminar diffusion flamelets for different scalar dissipation rate, whose predictability highly depends on the description of fuel–air mixing process in which engine mesh layout plays an important role. To this end, two grids were compared and assessed: in both grids, cells were aligned on the spray direction with such region being enlarged in the second one, where the near-nozzle and near-wall mesh resolution were also improved, which is expected to better account for both spray dynamics and flame–wall interaction dominating the combustion process in diesel engines. Flame structure, in-cylinder pressure, apparent heat release rate, and emissions for different relevant operating points were compared and analyzed to identify the most suitable mesh. Afterwards, simulations were carried out in a heavy-duty engine considering 20 operating points, allowing to comprehensively verify the validity of tabulated flamelet progress variable model. The results demonstrated that the proposed approach was capable to accurately predict in-cylinder pressure evolution and NO x formation across a wide engine map.