In recent years, hepatitis B core protein virus‐like particle (HBc VLP) is an impressive biomaterial, which has attracted considerable attention due to favorable properties such as structural stability, high uptake efficiency, and biocompatibility in biomedical applications. Heretofore, only a few attempts have been made to apply it in physical, chemical, and biological therapy for cancer. In this study, a tumor‐targeting RGD‐HBc VLP is first fabricated through genetic engineering. For image‐guided cancer phototherapy, indocyanine green (ICG) is loaded into RGD‐HBc VLP via a disassembly/reassembly pathway and electrostatic attraction with high efficiency. The self‐assembled stable RGD‐HBc VLP significantly improves body retention (fourfold longer), aqueous stability, and target specificity of ICG. Remarkably, these positive reformations promote more accurate and sensitive imaging of U87MG tumor, as well as prolonged tumor destruction in comparison with free ICG. Moreover, the photothermal and photodynamic effect on tumors are quantitatively differentiated by multiple linear regression analysis. Overall, less‐potent medicinal ICG can be perfectly rescued by bioengineered HBc VLP to realize enhanced cancer optotheranostics. A biosynthetic tumor‐targeting RGD‐peptide‐modified hepatitis B core particle is first loaded with indocyanine green (ICG) via disassembly/reassembly and the electrostatic attraction process to apply in cancer optotheranostics. Enhanced photoacoustic/fluoescence imaging and photothermal/photodynamic therapeutic efficacy are achieved because of the improvement in aqueous stability, body retention, and cellular uptake of ICG.