The clinical translation of ruthenium complexes as alternatives to platinum-based drugs is hindered by insufficient tumor targeting and limited therapeutic efficacy. Although nanodrug delivery systems (NDDS) offer potential solutions, existing Ru platforms often fail to integrate multi-modal therapeutic mechanisms effectively. This study aimed to construct a tumor-targeted Ru-Au nanoplatform, KKS-Ru@AuNPs, that synergizes Ru-based chemotherapy with photothermal therapy (PTT) to suppress tumor growth and metastasis simultaneously.The KKS-Ru@AuNPs system was developed by conjugating arginine-glycine-aspartic acid peptide-modified Ru complexes with Au nanospheres. The nanoscale properties of KKS-Ru@AuNPs were characterized utilizing transmission electron microscopy and nanoparticle size-measuring techniques. The photothermal performance of the KKS-Ru@AuNP system was assessed using near-infrared irradiation assays utilizing an infrared thermal imaging device. Additionally, anti-tumor efficacy was evaluated in an A549 xenograft mouse model, and tumor-targeting efficiency was quantified by inductively coupled plasma mass spectrometry (ICP-MS).The KKS-Ru@AuNPs exhibited nanospherical morphology, with nanospheres having a diameter of ~75 nm. Compared with AuNPs, KKS-Ru@AuNPs exhibited enhanced stability and superior photothermal conversion efficiency. Under in vitro conditions with irradiation using an 808 nm laser, the KKS-Ru@AuNPs exhibited significantly enhanced cytotoxic effects. In vivo studies revealed that KKS-Ru@AuNPs achieve greater tumor accumulation than that achieved by AuNPs. The synergistic therapeutic effect of KKS-Ru@AuNPs was evidenced by an 84.6% reduction in tumor weight and a 46% decrease in the number of lung metastatic nodules.This study established a Ru-based NDDS by integrating active targeting, chemotherapy, and PTT into a single platform, overcoming the limitations of conventional monotherapeutic approaches. However, challenges persist in terms of long-term biosafety due to hepatic Au accumulation and tumor heterogeneity-dependent targeting efficiency. Future studies should focus on degradable carrier designs and multi-omics mechanistic analysis to promote clinical applicability of Ru-based NDDSs.© 2025 Zhu et al.