Health Technology Assessment (HTA) is a multidisciplinary, systematic process for evaluating the safety, efficacy, cost-effectiveness, and broader social and ethical implications of health technologies—including drugs, devices, clinical procedures, and organizational systems. By combining clinical evidence, economic modeling, and stakeholder perspectives, HTA guides decisions on adoption, reimbursement, and optimal use, ensuring that limited resources deliver maximum value. Established agencies such as NICE in the UK and HAS in France have institutionalized HTA at the national level, while hospitals increasingly deploy streamlined “mini-HTA” units to inform frontline choices in specific departments. For example, HTA analyses of implantable cardioverter-defibrillators (ICDs) identified patient subgroups for whom benefits justify high costs, shaping targeted reimbursement policies. Similarly, evaluations of robotic surgery systems demonstrated significant advantages only in high-volume centers, leading to recommended specialization rather than indiscriminate diffusion. HTA thus drives both innovation and sustainability by distinguishing high-value from low-value interventions. Contemporary HTA also integrates real-world evidence, horizon scanning, and ethical, legal, and social impact assessments, as in the case of non-invasive prenatal testing, where informed consent and equity concerns shaped implementation frameworks. Patient and public involvement further enriches relevance and legitimacy. As healthcare faces aging populations, rising chronic disease burdens, and fiscal constraints, HTA offers a robust evidence-based framework to balance innovation, efficiency, and equity—ensuring that new technologies improve outcomes without compromising sustainability.