Peritoneal metastases are growths that arise from the shedding and implantation of cancerous cells from ovarian, gastric, colorectal or extraperitoneal (breast, lung) origin in the peritoneal cavity [1]. These metastases are typically treated through combination therapies such as surgery and chemotherapy. However, full tumor resection is challenging, and the incomplete removal of cancerous tissue can lead to recurrence in the patient. Thus, there is a need for fluorescent guided probes for use in tumor resection as they offer high specificity and real-time capabilities [2]. Nanocarriers have the potential to deliver drugs and imaging tracers to tumor sites and accumulate at targeted locations, allowing for improved diagnosis and therapy. Ultrasmall Porous Silica Nanoparticles (UPSNs) (hydrodynamic diameter (HD) ~ 15 nm) have demonstrated enhanced tumor uptake, evasion and timely hepatobiliary clearance profile [3]. We synthesized the UPSNs and evaluated them for size, surface charge, and morphology using Dynamic Light scattering and Transmission electron microscopy. Surface modification of UPSN with polyethylene glycol (PEG) allowed long blood circulation and amine groups provide facile chemistry for conjugation. Stability of UPSNs were monitored at 4°C and 25°C to assess the shelf life under different storage conditions. UPSNs were tested in animal models of cancer metastasis. Results: UPSNs maintain stability for up to 90 days at both 4°C (HD: 17.65 ± 2.82 nm, PDI 0.026 ± 0.0056) and 25°C (HD: 12.81 ± 3.46, PDI 0.078 ± 0.02). Biodistribution assessment of Cy5 conjugated particles (UPSN-Cy5) in mouse models of peritoneal metastasis of gastric cancer using optical imaging suggested the selective uptake of UPSN-Cy5 in tumors with improved specificity compared to ICG, an FDA-approved fluorescent probe, allowing for complete resection of metastatic tumor nodules in all mice tested. Overall, UPSN have the potential to serve as a powerful tool for localized and precise treatment of cancer through fluorescent molecular-guided surgery.