A mathematical model for failure prediction and reliability assessment of coating-substrate system is developed based on a multidisciplinary approach. Two models for diffusion and bending of bi-layer cantilever beam have been designed separately based on the concepts of material science and solid mechanics respectively. Then, these two models are integrated to design an equation for debonding driving force under mesomechanics concepts. Mesomechanics seeks to apply the concepts of solid mechanics to microstructural constituent of materials such as coatings. This research takes the concepts of mesomechanics to the next level in order to predict the performance and assess the reliability of coatings based on the measure of debonding driving force. The effects of two parameters i.e. interface roughness and coating thickness on debonding driving force have been analysed using finite difference method. Critical/threshold value of debonding driving force is calculated which defines the point of failure of coating-substrate system and can be used for failure prediction and reliability assessment by defining three conditions of performance i.e. safe, critical and fail. Results reveal that debonding driving force decreases with an increase in interface roughness and coating thickness. However, this is subject to condition that the material properties of coating such as diffusivity should not increase and Young's modulus should not decrease with an increase in the interface roughness and coating thickness. The model is based on the observations recorded from experimentation. These experiments are performed to understand the behaviour of debonding driving force with the variation in interface roughness and coating thickness.