NASA is broadly pursuing a digital transformation strategy across the junctures of its missions, technology, workforce, stakeholders and infrastructure. NASA is formulating its digital transformation strategy through six strategic thrust areas or digital building blocks of transformation. The digital transformation strategy is cross-cutting to escape silos and includes a thrust designated as “model-based everything” where digital models are integrated together and are projected to be the future standard of enterprise-wide functions. The digital twin methodology is foundational to understanding and integration of modeling and simulation across all of NASA’s ambitious thrusts of the transformation. The digital twin is interdisciplinary, integrating knowledge and methods from different disciplines and using a synthesis of approaches to enable synchronized decision-making with increasing complexity, velocity, confidence, and adaptability. John Vickers, one of the originators of the digital twin concept, will discuss priorities, challenges and use cases for NASA’s imperative of a digital twin-driven ecosystem.