Neuroimmunology is reshaping the understanding of the central nervous system (CNS), revealing it as an active immune organ rather than an isolated structure. This review delves into the unprecedented discoveries transforming the field, including the emerging roles of microglia, astrocytes, and the blood–brain barrier (BBB) in orchestrating neuroimmune dynamics. Highlighting their dual roles in both repair and disease progression, we uncover how these elements contribute to the intricate pathophysiology of neurodegenerative diseases, cerebrovascular conditions, and CNS tumors. Novel insights into microglial priming, astrocytic cytokine networks, and meningeal lymphatics challenge the conventional paradigms of immune privilege, offering fresh perspectives on disease mechanisms. This work introduces groundbreaking therapeutic innovations, from precision immunotherapies to the controlled modulation of the BBB using nanotechnology and focused ultrasound. Moreover, we explore the fusion of immune modulation with neuromodulatory technologies, underscoring new frontiers for personalized medicine in previously intractable diseases. By synthesizing these advancements, we propose a transformative framework that integrates cutting-edge research with clinical translation, charting a bold path toward redefining CNS disease management in the era of precision neuroimmunology.