During the last decade, artificial intelligence (AI) has enabled key technological innovations within the modern dementia and frailty healthcare and prevention landscape. This has boosted the impact of technology in the clinical setting, enabling earlier diagnosis with improved specificity and sensitivity, leading to accurate and time-efficient support that has driven the development of preventative interventions minimizing the risk and rate of progression. Background/Objectives: The rapid ageing of the European population places a substantial strain on the current healthcare system and imposes several challenges. COMFORTage is the joint effort of medical experts (i.e., neurologists, psychiatrists, neuropsychologists, nurses, and memory clinics), social scientists and humanists, technical experts (i.e., data scientists, AI experts, and robotic experts), digital innovation hubs (DIHs), and living labs (LLs) to establish a pan-European framework for community-based, integrated, and people-centric prevention, monitoring, and progression-managing solutions for dementia and frailty. Its main goal is to introduce an integrated and digitally enabled framework that will facilitate the provision of personalized and integrated care prevention and intervention strategies on dementia and frailty, by piloting novel technologies and producing quantified evidence on the impact to individuals’ wellbeing and quality of life. Methods: A robust and comprehensive design approach adopted through this framework provides the guidelines, tools, and methodologies necessary to empower stakeholders by enhancing their health and digital literacy. The integration of the initial information from 13 pilots across 8 European countries demonstrates the scalability and adaptability of this approach across diverse healthcare systems. Through a systematic analysis, it aims to streamline healthcare processes, reduce health inequalities in modern communities, and foster healthy and active ageing by leveraging evidence-based insights and real-world implementations across multiple regions. Results: Emerging technologies are integrated with societal and clinical innovations, as well as with advanced and evidence-based care models, toward the introduction of a comprehensive global coordination framework that: (a) improves individuals’ adherence to risk mitigation and prevention strategies; (b) delivers targeted and personalized recommendations; (c) supports societal, lifestyle, and behavioral changes; (d) empowers individuals toward their health and digital literacy; and (e) fosters inclusiveness and promotes equality of access to health and care services. Conclusions: The proposed framework is designed to enable earlier diagnosis and improved prognosis coupled with personalized prevention interventions. It capitalizes on the integration of technical, clinical, and social innovations and is deployed in 13 real-world pilots to empirically assess its potential impact, ensuring robust validation across diverse healthcare settings.