Dynamic performance and lifespan predictions are essential for understanding the whole life-cycle emissions and environmental impacts of landfills. However, there are knowledge gaps regarding the major failure modes and mechanisms in flexible hazardous waste landfills (FHWLs) and their potential effects on the service life of landfills. These issues limit the advancement of related research. In this study, focusing on flexible landfills, failure mode, mechanism, and effects analysis was conducted to identify the major failure modes, mechanisms, and impacts that may occur in landfills under extremely harsh chemical and stress conditions. The results indicate that there are approximately 33 major components and materials in landfills, corresponding to 35 potential failure modes and more than 60 underlying failure mechanisms. Notably, the failure of the drainage media in the drainage system is concerning and challenging to recover from. In contrast, the failure of the high-density polyethylene geomembrane (HDPE GMB) in the liner system (LS) is considered serious and is prone to occur, but it is also difficult to detect. Therefore, these two failure modes were identified as critical factors affecting the degradation of the performance and longevity of FHWLs. Finally, due to their high probability of occurrence and severe impacts, stress damage (physical damage) and oxidative aging were identified as the main degradation modes of HDPE GMB, the core material in FHWLs. This study provides key insights into performance prediction targets, failure modes, and failure mechanisms for further research on long-term landfill performance and life prediction. It prompts the government and stakeholders to re-examine the rationality behind the positioning of landfills, such as the assumptions of unlimited service and solid waste management endpoints. Therefore, it calls for a reassessment and optimization of the full life cycle emissions of landfills and related waste.