Thermal barrier coatings (TBCs) represent a relatively thin layer of ceramic with the favourable insulating properties, which are generally used to improve the temperature stability of the engineering component such as turbine blades. One of the prime prerequisites of TBCs is to determine the optimised coating configuration with the desired thermo-mechanical properties and enhanced service life. In a typical functionally graded coating structure, this could be achieved by having a trade-off between the thermal insulation and fatigue toughness offered by ceramic in top coat and metal towards the substrate, respectively. In this work, a computational method was used to analyse and optimise the parameters pertaining to thermo-mechanical evaluation of the slurry spray-coated (SST) mullite–nickel ASTM 1018 steel. The composite material properties have been predicted using the classical mean-field micromechanics model and rule of mixtures and the finite element simulation package ANSYS. Experimental validation has been performed to analyse the relative thermal and structural properties of the composite layers of the coatings using transient plane source (TSP)-based thermal constants analyser. The predicted and experimental results were further analysed and optimised for various process parameters using response surface optimisation and multi-objective genetic algorithm, which evaluated the optimum results considering the boundary conditions with a temperature reduction of nearly 306 °C. Further, the research results indicate that suitable thickness of the coating configuration of the slurry-sprayed mullite–nickel TBC system included coating thickness of 57.2 μm, 147.1 μm, and 143.9 μm for bond, intermediate, and top coats, respectively. The material properties were found dependent on the coating composition across the FG structure, and the predicted, computed, and experimental results were in reasonable agreement.