<p>Brain tumors are among the most lethal forms of cancer, often presenting treatment challenges due to the complexity of the central nervous system and the restrictive nature of the blood–brain barrier (BBB). Superparamagnetic iron oxide nanoparticles (SPIONs) have emerged as promising agents in neuro-oncology due to their unique magnetic properties, biocompatibility, and multifunctional capabilities. SPIONs serve as potent contrast agents in magnetic resonance imaging (MRI), drug delivery vehicles, and hyperthermia mediators. Their ability to be functionalized with ligands and antibodies allows for targeted delivery, minimizing systemic toxicity and enhancing therapeutic precision. Moreover, SPIONs have shown potential in modulating immune responses, disrupting tumor microenvironments, and improving the delivery of chemotherapeutics across the BBB. Despite encouraging preclinical outcomes and some early-phase clinical trials, challenges such as biodistribution control, toxicity, and manufacturing scalability remain. This review highlights the current landscape of SPION applications in brain tumor therapy and diagnosis, elaborating on their synthesis, functionalization, and translational hurdles. We also discuss future directions, including AI-guided theranostics, personalized nanomedicine, and integration with immunotherapy, aiming to illuminate the path forward for SPION-based clinical interventions.</p> Graphical Abstract <p>SPIONs for Diagnosis and Therapy of Brain Tumors</p> <p></p>