This study presents a novel approach for tumor resection and photothermal therapy (PTT) using gold molecular clusters (AuPC) functionalized with phosphorylcholine ligands. The AuPC clusters, which are ~2 nm in size, are intratumorally injected and exhibit strong NIR-II/SWIR (1,000–3,000 nm) fluorescence imaging properties, enabling precise tumor margin delineation and resection. The clusters are stealthy, with a phosphocholine coating that allows them to homogeneously fill the tumor interstitial fluid space. This uniform distribution facilitates both imaging-guided surgery and PTT, as the clusters can uniformly heat and eradicate tumors. In vivo NIR-IIb molecular imaging using a quantum dot-Annexin V (QD-P³-Anx V) conjugate revealed cancer cell apoptosis following PTT. The AuPC clusters also demonstrated rapid renal excretion, high biocompatibility, and safety, making them promising for clinical translation. The study highlights the potential of AuPC as a versatile agent for both imaging-guided surgery and PTT in preclinical models of 4T1 murine breast cancer. The results demonstrate that AuPC can effectively guide tumor resection, achieve complete tumor eradication, and monitor apoptosis in tumors. The uniform distribution of AuPC within the tumor and its interstitium, along with its application in NIR-II PTT, positions the clusters as a promising candidate for clinical translation. The study also underscores the importance of intratumoral administration in overcoming the limitations of systemic delivery, such as off-target toxicity and uneven drug distribution. The findings suggest that AuPC could be a valuable tool for improving cancer treatment outcomes through enhanced imaging and targeted therapy.This study presents a novel approach for tumor resection and photothermal therapy (PTT) using gold molecular clusters (AuPC) functionalized with phosphorylcholine ligands. The AuPC clusters, which are ~2 nm in size, are intratumorally injected and exhibit strong NIR-II/SWIR (1,000–3,000 nm) fluorescence imaging properties, enabling precise tumor margin delineation and resection. The clusters are stealthy, with a phosphocholine coating that allows them to homogeneously fill the tumor interstitial fluid space. This uniform distribution facilitates both imaging-guided surgery and PTT, as the clusters can uniformly heat and eradicate tumors. In vivo NIR-IIb molecular imaging using a quantum dot-Annexin V (QD-P³-Anx V) conjugate revealed cancer cell apoptosis following PTT. The AuPC clusters also demonstrated rapid renal excretion, high biocompatibility, and safety, making them promising for clinical translation. The study highlights the potential of AuPC as a versatile agent for both imaging-guided surgery and PTT in preclinical models of 4T1 murine breast cancer. The results demonstrate that AuPC can effectively guide tumor resection, achieve complete tumor eradication, and monitor apoptosis in tumors. The uniform distribution of AuPC within the tumor and its interstitium, along with its application in NIR-II PTT, positions the clusters as a promising candidate for clinical translation. The study also underscores the importance of intratumoral administration in overcoming the limitations of systemic delivery, such as off-target toxicity and uneven drug distribution. The findings suggest that AuPC could be a valuable tool for improving cancer treatment outcomes through enhanced imaging and targeted therapy.