This study introduces multifunctional silica nanoparticles that exhibit both high photothermal and chemodynamic therapeutic activities, in addition to luminescence. The activity of the silica nanoparticles is derived from their plasmonic properties, which are a result of infusing the silica nanoparticles with multiple Cu_2–xS cores. This infusion process is facilitated by a recoating of the silica nanoparticles with a cationic surfactant. The key factors that enable the internal incorporation of the Cu_2–xS cores and the external deposition of red-emitting carbon dots are identified. The Cu_2–xS cores within the silica nanoparticles exhibit both self-boosting generation of reactive oxygen species and high photothermal conversion efficacy, which are essential for photothermal and chemodynamic activities. The silica nanoparticles’ small size (no more than 70 nm) and high colloidal stability are prerequisites for their cell internalization. The internalization of the red-emitting silica nanoparticles within cells is visualized using fluorescence microscopy techniques. The chemodynamic activity of the silica nanoparticles is associated with their dark cytotoxicity, and the mechanisms of cell death are evaluated using an apoptotic assay. The photothermal activity of the silica nanoparticles is demonstrated by significant cell death under near-infrared (1064 nm) irradiation.