The development of fan-out packaging technology for fine-pitch and high-pin-count applications is a hot topic in semiconductor research. To reduce the package footprint and improve system performance, many applications have adopted packaging-on-packaging (PoP) architecture. Given its inherent characteristics, glass is a good material for high-speed transmission applications. Therefore, this study proposes a fan-out wafer-level packaging (FO-WLP) with glass substrate-type PoP. The reliability life of the proposed FO-WLP was evaluated under thermal cycling conditions through finite element simulations and empirical calculations. Considering the simulation processing time and consistency with the experimentally obtained mean time to failure (MTTF) of the packaging, both two- and three-dimensional finite element models were developed with appropriate mechanical theories, and were verified to have similar MTTFs. Next, the FO-WLP structure was optimized by simulating various design parameters. The coefficient of thermal expansion of the glass substrate exerted the strongest effect on the reliability life under thermal cycling loading. In addition, the upper and lower pad thicknesses and the buffer layer thickness significantly affected the reliability life of both the FO-WLP and the FO-WLP-type PoP.