The early 2000s to the early 2010s marked a shift from single-modality studies toward integrated multimodal imaging workflows that fuse structural, functional, and molecular information across modalities such as positron emission tomography-magnetic resonance imaging (PET-MRI), computed tomography, and fluorescence techniques. Methodological emphasis grew on simultaneous or harmonized data acquisition, robust fusion strategies, and end-to-end workflows, complemented by a surge in open-source software and platforms that democratized multimodal image analysis. Clinically, research moved toward standardized multimodal workflows, cross-disciplinary collaboration, and the groundwork for translational adoption, setting the stage for routine cross-modality interpretation in practice. Historical Significance: This period established many foundational principles for true multimodal integration, exemplified by the emergence of integrated PET-MRI workflows and multiscale fusion approaches that preserve cross-modality features. The advent of open software tools for multimodal analysis and durable guidelines for cardiovascular and other organ system imaging created a shared infrastructure that shaped subsequent advances in molecular imaging and translational research.