The concept of a digital twin is intriguing as it presents an innovative approach to solving numerous real-world challenges. Initially emerging from the domains of manufacturing and engineering, digital twin research has transcended its origins and now finds applications across a wide range of disciplines. This multidisciplinary expansion has impressively demonstrated the potential of digital twin research. While the simulation aspect of a digital twin is often emphasized, the role of artificial intelligence (AI) and machine learning (ML) is severely understudied. For this reason, in this paper, we highlight the pivotal role of AI and ML for digital twin research. By recognizing that a digital twin is a component of a broader Digital Twin System (DTS), we can fully grasp the diverse applications of AI and ML. In this paper, we explore six AI techniques—(1) optimization (model creation), (2) optimization (model updating), (3) generative modeling, (4) data analytics, (5) predictive analytics and (6) decision making—and their potential to advance applications in health, climate science, and sustainability.