Microelectronic systems such as cell phones, computers, consumer electronics, and implantable medical devices consist of subsystems which in turn consist of other subsystems and components. When such systems are designed, fabricated, assembled, and tested, they need to meet reliability, cost, performance, and other targets for being competitive. The design of reliable electronic packaging systems in a systematic and timely manner requires a consistent and unified method for allocating, predicting, and assessing reliability and for recommending design changes at the component and system level with consideration of both random and wearout failures. Accordingly, this dissertation presents a new unified knowledge modeling method for System Design for Reliability (SDfR) called the Reliability Object Model (ROM) method. The ROM method consistently addresses both reliability allocation and assessment for systems composed of series and parallel subsystems. The effectiveness of the ROM method has been demonstrated for allocating, predicting, and assessing reliability, and the results show that ROM is more effective compared to existing methods, providing richer semantics, unified techniques, and improved SDfR quality. Furthermore, this dissertation develops representative reliability metrics for random and wearout failures, and incorporates such metrics into ROM together with representative algorithms for allocation, assessment, and design change recommendations. Finally, this research implemented the ROM method in a computing framework and demonstrated its applicability using several relevant microelectronic system test cases and prototype SDfR tools.