In the context of carbon neutrality, the large-scale commercialization of clean-energy generation demands an innovative engineering paradigm that can ensure the reliability and durability of the associated critical mechanical equipment. In this study, structural-integrity challenges that are encountered during the clean-energy transition were investigated, and advancements in accurate lifetime-design methodologies were explored. This study addressed the complexities of multi-mode damage interactions and demonstrated the effects of such interactions on the critical mechanical equipment. By tracking the evolution of lifetime-design approaches, the fundamental aspects of damage-driven lifetime-design methodologies were determined. A case study that involved creep-fatigue-oxidation interactions demonstrated the simplicity and high accuracy of the modeling methodology that was developed during this study for industrial applications. To evaluate the carbon-reduction benefits that are associated with lifetime extension, a three-level quantitative criterion, which links prediction scatter, extension potential, and net emissions reduction, was developed. Hierarchical Bayesian modeling was also implemented to capture multi-level uncertainties across various regions and energy types, thereby providing probabilistic insights into diverse operational scenarios. In the future, accurate lifetime design is expected to be integrated into a full-chain technical tetrahedron for structural-integrity evaluations; thus, it will redefine the role of engineering in the design, manufacture, operation, and maintenance of mechanical equipment that is critical for a sustainable future.