The Division of Mathematical Sciences (DMS) in the Directorate for Mathematical and Physical Sciences (MPS) at the National Science Foundation (NSF) and the Air Force Office of Scientific Research (AFOSR) plan to jointly support foundational mathematical and statistical research on Digital Twins in applied sciences. Recent years have witnessed a significant increase in the demand and interest in applications that involve collaborative teams developing and analyzing Digital Twins to support decision making in various fields, including science, engineering, medicine, urban planning, and more. Both agencies recognize the need to promote research aiming to stimulate an interplay between mathematics/ statistics/ computation and practical applications in the realm of Digital Twins. This program encourages new collaborative efforts within the realm of Digital Twins, aiming at stimulating fundamental research innovation, pushing, and expanding the boundaries of knowledge, and exploring new frontiers in mathematics and computation for Digital Twin development, and its applications. By leveraging this synergy, the program aims to harness science, technology, and innovation to address some of our Society's most pressing challenges.