<p>Selenium nanoparticles (SeNPs) have been given special attention as a promising nanoplatform in contemporary cancer therapeutics, owing to their intrinsic redox activity, biocompatibility, and selective cytotoxicity toward malignant cells. Unlike traditional selenium compounds, SeNPs exhibit enhanced bioavailability and reduced systemic toxicity, making them a safer alternative for clinical applications. SeNPs demonstrate multifaceted biological actions—including apoptosis induction, angiogenesis inhibition, metastasis suppression, and tumor microenvironment modulation—thus positioning them as versatile agents in precision oncology. Their surface can be readily functionalized with targeting ligands, polymers, and therapeutic agents to improve specificity and efficacy. When compared with other nanoparticles, SeNPs offer distinct advantages. Gold nanoparticles (AuNPs), while widely used for drug delivery and photothermal therapy, are expensive and may persist in tissues due to limited biodegradability. Silver nanoparticles (AgNPs) exhibit potent cytotoxicity through the generation of reactive oxygen species, but often lack selectivity, resulting in collateral damage to healthy cells. Iron oxide nanoparticles (IONPs), favored for magnetic targeting and imaging, can induce oxidative stress and require external activation. In contrast, SeNPs provide a balanced profile of efficacy, safety, and biodegradability. Recent innovations in SeNP synthesis, particularly via green methods utilizing plant extracts and biomolecules, have enhanced sustainability and reproducibility. This review explores SeNP synthesis, characterization, mechanisms of action, and integration with drug delivery systems and combinatorial therapies. By comparing SeNPs with other nanoplatforms, it critically evaluates their translational potential and underscores their promise as a transformative tool in cancer nanomedicine.</p>