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Plenary Two from the HTAi 2025 Annual Meeting: NextGen Methods: Hype Or Here To Stay? Building on the insights from Plenary 1, which will examine how emerging technologies are reshaping healthcare and the challenging demands HTA is facing globally, Plenary 2 shifts the focus to the next-generation methods essential for HTA to respond effectively to new innovations and health system needs. As the healthcare landscape evolves, there is a need for adaptive approaches that keep HTA relevant and impactful, moving beyond traditional roles to becoming a proactive force in decision-making. Practical and implementable methods that align with the rapid pace of innovation are essential to ensure HTA continues to meet the needs of decision-makers and health system partners across diverse healthcare settings. Next-generation methods include artificial intelligence (AI) applications in predictive modeling and the assessment of evidence for digital health and personalized medicine. The strengths and limitations of innovative trial designs and how AI can enhance efficiencies in HTA practices will be examined, such as automating evidence synthesis and managing large datasets. The aim is to understand what methods are needed to keep pace with technological advancements and to critically examine when these methods are needed, ensuring that HTA remains adaptable and effective in evaluating modern healthcare innovations. The focus extends to identifying the most practical tools for engagement and examining how the evolution of HTA can adapt to address broader factors like environmental impacts, equity, and ethics. Emphasis is placed on adaptive HTA—tailoring methods to fit diverse contexts, from high-income countries to low- and middle-income nations, ensuring that HTA remains relevant and impactful on a global scale. Emerging methods for assessing critical HTA domains, such as environmental impacts, equity, ethics, and the integration of real-world evidence into HTA practices are also highlighted. The need for a more comprehensive approach to evaluating the sustainability of healthcare technologies and delivery systems becomes clear, with attention on how effectively current methods address these growing concerns. Inclusive and effective engagement with decision-makers remains a priority, particularly in regions where HTA integration into decision-making processes is still developing. Opportunities exist to employ innovative visualization techniques to better communicate uncertainties in evidence and support performance-based or outcomes-based agreements. Enhancing the impact of HTA depends on clear and effective communication of complex technologies and evidence, ensuring it is both accessible and actionable for decision-makers and health system partners. In summary, Plenary 2 will generate a thought-provoking discussion on innovative and adaptive methods that support robust and sustainable HTA activities, meeting the diverse needs of health systems globally. Key questions to be explored include: What next-generation methods are needed by HTA organizations? How can AI enhance HTA processes, from evidence synthesis to predictive modelling? What approaches can integrate new data sources to enhance horizon scanning and related HTA practices? How will HTA adapt evidence standards to emerging trial designs and diverse sources of real-world evidence? In what ways can next-generation methods be incorporated into current regulatory and HTA practices? A range of perspectives will be showcased to keep HTA at the forefront of evidence-based decision-making, focusing on next-generation methods that are poised to endure beyond initial hype.