The interplay between residual stress state, cohesive and adhesive properties of coatings on substrates is reviewed in this article. Attention is paid to thin inorganic coatings on polymers, characterized by a very high hygro-thermo-mechanical contrast between the brittle and stiff coating and the compliant and soft substrate. An approach to determine the intrinsic, thermal and hygroscopic contributions to the coating residual stress is detailed. The critical strain for coating failure, coating toughness and coating/substrate interface shear strength are derived from the analysis of progressive coating cracking under strain. Electrofragmentation and electro-fatigue tests in situ in a microscope are described. These methods enable reproducing the thermo-mechanical loads present during processing and service life, hence identifying and modeling the critical conditions for failure. Several case studies relevant to food and pharmaceutical packaging, flexible electronics and thin film photovoltaic devices are discussed to illustrate the benefits and limits of the present methods and models.