Biodegradable silicate nanoconstructs have aroused tremendous interest in cancer therapeutics due to their variable framework composition and versatile functions. Nevertheless, low intratumoral retention still limits their practical application. In this study, oxygen vacancy (OV)-enriched bimetallic silicate nanozymes with Fe-Ca dual active sites via modification of oxidized sodium alginate and gallic acid (GA) loading (OFeCa-V@GA) were developed for targeted aggregation-potentiated therapy. The band gap of silica markedly decreased from 2.76 to 1.81 eV by codoping of Fe and Ca, enabling its excitation by a 650 nm laser to generate reactive oxygen species. The OV that occurred in the hydrothermal synthetic stage of OFeCa-V@GA can anchor the metal ions to form an atomic phase, offering a massive fabrication method of single-atom nanozymes. Density functional theory results reveal that the Ca sites can promote the adsorption of HO and Fe sites can accelerate the dissociation of HO, thereby realizing a synergetic catalytic effect. More importantly, the targeted delivery of metal ions can induce a morphological transformation at tumor sites, leading to high retention (the highest retention rate is 36.3%) of theranostic components in tumor cells. Thus, this finding may offer an ingenious protocol for designing and engineering highly efficient and long-retention nanodrugs.