This study introduces Au25 molecular clusters functionalized with phosphorylcholine ligands (AuPC) as a preclinical intratumorally injectable agent for near-infrared-II (NIR-II) fluorescence imaging-guided tumor resection and photothermal therapy (PTT). The AuPC clusters were found to uniformly distribute in 4T1 murine breast cancer tumors upon intratumor (i.t.) injection, with a significant fraction entering the tumor interstitial fluid space. This uniform distribution allowed for clear delineation of tumor margins and complete, non-excessive tumor resection guided by NIR-II imaging. The AuPC clusters also served as effective PTT agents, uniformly heating and eradicating tumors. In vivo NIR-IIb molecular imaging using a quantum dot-Annexin V conjugate revealed cancer cell apoptosis following PTT. The therapeutic functionalities of AuPC clusters, combined with rapid renal excretion, high biocompatibility, and safety, make them promising for clinical translation.This study introduces Au25 molecular clusters functionalized with phosphorylcholine ligands (AuPC) as a preclinical intratumorally injectable agent for near-infrared-II (NIR-II) fluorescence imaging-guided tumor resection and photothermal therapy (PTT). The AuPC clusters were found to uniformly distribute in 4T1 murine breast cancer tumors upon intratumor (i.t.) injection, with a significant fraction entering the tumor interstitial fluid space. This uniform distribution allowed for clear delineation of tumor margins and complete, non-excessive tumor resection guided by NIR-II imaging. The AuPC clusters also served as effective PTT agents, uniformly heating and eradicating tumors. In vivo NIR-IIb molecular imaging using a quantum dot-Annexin V conjugate revealed cancer cell apoptosis following PTT. The therapeutic functionalities of AuPC clusters, combined with rapid renal excretion, high biocompatibility, and safety, make them promising for clinical translation.