Presently, there are several challenges that need to be overcome in the development of treatments that can effectively inhibit tumor growth, prevent the spread of tumor metastases, and protect the host against recurrence. Accordingly, a powerful synergistic immunotherapy method was developed to achieve the treatment of cancer. Herein, we established an improvement in the nanoengineering of gold nanorod (GNR)-mediated photothermal therapy (PTT) with theranostic indocyanine green (ICG), which also produced heat for effective PTT under near-infrared (NIR) light. Furthermore, co-encapsulated resiquimod (R848) induced the activation of an immune response against the tumor. In addition, a nuclear-targeted transactivator of transcription (TAT) peptide conjugated with FA-functionalized GNRs was produced for intranuclear tumor-targeted in vivo photothermal therapeutic efficacy, inducing DAMPs for immunogenic cell death (ICD). Post-PTT release of R848-activated TLR7/8 is essential for the development of a potent antitumor immune response by increasing the number of T cells, which recognize and kill tumors. Thus, this integrated immunotherapy method can be utilized for both the diagnosis and treatment of tumor recurrence, providing novel opportunities for both basic and clinical research. Collectively, our findings suggest that nanotechnology may be a useful technique for improving the efficacy of vaccine-based cancer immunotherapy.