In an increasingly digital and interconnected world, information systems play a pivotal role in shaping organizational success. The strategic use of IS enables businesses to enhance operational efficiency, foster innovation, and maintain a competitive edge in dynamic markets. However, leveraging IS effectively requires more than just technological adoption—it necessitates a robust framework for strategy and governance. This chapter provides an in-depth exploration of IS Strategy and Governance, delving into foundational theories, established models, and practical applications. It examines the critical role of IS in achieving strategic business objectives and underscores the importance of aligning IT initiatives with broader organizational goals. Frameworks such as the Henderson and Venkatraman Strategic Alignment Model offer insights into aligning IT with business strategy, ensuring that technology investments deliver tangible value. Moreover, this chapter highlights modern governance approaches that address emerging trends and challenges, such as cybersecurity threats, sustainability requirements, and the shift to remote work. By integrating traditional methodologies with contemporary practices, organizations can build resilient and adaptive IS frameworks capable of navigating the complexities of today’s business landscape.