Abstract: Superparamagnetic iron oxide nanoparticles (SPIONs) have been shown to exhibit degradability, superparamagnetic responsiveness, and multimodal functional properties, which are expected to overcome the bottleneck of traditional separation between diagnosis and treatment in the time and space domains. Through magnetic resonance imaging (MRI)-guided intelligent delivery of targeted drugs, magnetic/light/acoustic multi-physical field collaborative therapy, and other strategies, the tumor microenvironment can be precisely regulated and drug resistance can be reversed. Herein, we systematically review the core mechanisms of SPIONs in cross-scale diagnosis and treatment and discuss the innovative application mechanism and technical progress of SPIONs in regard to the integration of tumor theranostics. SPIONs provide breakthrough solutions for the precise diagnosis and treatment of tumors through MRI navigation, targeted delivery system construction, and multimodal strategies, offering a theoretical foundation. However, current studies continue to encounter various challenges, including inadequate biosafety validation, restricted efficiency of targeted delivery due to tumor heterogeneity, and complexity of optimizing parameters for multimodal synergistic treatments. Further refinement of material design and clinical translation strategies are essential for providing a valuable reference for developing systematic solutions that bridge theoretical innovations with technological implementation in tumor precision medicine.