AI-empowered learning tools enhance student engagement through personalised educational support and collaborations that enhance academic performance. The growing presence of artificial intelligence (AI)-powered learning tools necessitates a closer look at their design. Numerous studies have demonstrated the growing application of AI in human–computer interaction (HCI) technology within the context of higher education. However, there are few studies on the impact of AI-powered learning and HCI design principles and transhumanism on cognitive processes and well-being of learners. It is thus necessary to examine the benefits and ethical implications of integrating HCI design principles into developing effective and inclusive AI-powered learning tools. Drawing on social and emotional learning (SEL), transhumanistic, and technology-human interaction perspectives, the chapter explores the role of AI-powered tools in education, design principles of HCI, and transhumanism on cognitive learning and well-being of learners. Based on hermeneutic literature review, the chapter draws from a range of existing studies published between 2010 and 2024 from ProQuest, Google scholar, Scopus, and Web of Science databases. A total of 115 studies were sourced for analysis. The review revealed three sets of challenges, namely, general concerns and ethical challenges; lack of human-centred approach, unclear pedagogical principles; and risks HCI design principles as well as transhumanistic incongruency. Drawing from these challenges, recommendations for the responsible use of AI in education through human-centred AI in education framework (HCAI) are proposed.