This book constitutes the refereed proceedings of the 5th International Conference on Dynamic Data Driven Applications Systems, DDDAS/Infosymbiotics for Reliable AI 2024, held in New Brunswick, NJ, USA, during November 6–8, 2024. The 43 full papers included in this book were carefully reviewed and selected from 52 submissions. By combining DDDAS and typical AI approaches, the papers address state-of-the-art efforts to create frameworks for enabling new and advanced Science and Technology capabilities to address challenges and create opportunities in important areas, spanning a wide set of areas, such as: materials and aerospace systems; communications networks; energy infrastructures; cyber-security; adverse environmental situations; societal dynamics; computer vision; robotics; laboratory automation; bio-informatics and pharmaceuticals design; and more.