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Pheochromocytoma and paraganglioma (PPGL) are rare neuroendocrine tumors characterized by remarkable clinical heterogeneity and genetic complexity. Conventional diagnostic and therapeutic strategies have largely relied on catecholamine assessment, anatomical imaging, and surgical resection; however, these approaches exhibit substantial limitations in metastatic risk stratification and personalized management for metastatic PPGL. Advances in genomics have enabled the establishment of the molecular cluster classification for PPGL, including pseudohypoxic, kinase-signaling, and Wnt-altered clusters, and corresponding strategies for precise nuclear medicine imaging and tumor surveillance. Recently, the refined application of nuclear medicine molecular imaging, the publication of international consensus guidelines on the management of patients with SDHB and SDHD mutations, and the approval of the hypoxia-inducible factor-2α (HIF-2α) inhibitor belzutifan, collectively have marked the entry of PPGL management into the era of precision medicine. Nonetheless, molecular cluster-guided targeted therapies for metastatic PPGL have not yet been incorporated into clinical guidelines, due to poorly characterized molecular mechanisms, a lack of patient-derived preclinical models, and the absence of cluster-specific, head-to-head clinical trials. Looking forward, the precision medicine in PPGL will move toward refined molecular subtyping, individualized treatment, integrated theranostic approaches, and multicenter collaboration.