Abstract Partial nephrectomy is becoming an increasingly important treatment for kidney cancer because more than 60% of kidney cancer cases are diagnosed in early, localized stages. Compared to radical nephrectomy, partial nephrectomy offers much better preservation of renal function while having an equivalent oncological efficacy for the localized kidney cancer, thereby significantly reducing the postoperative risk of chronic kidney disease, kidney failure and cardiovascular events. However, accurate visualization of renal tumor and its boundary remains a long-standing technique challenge. Although intraoperative near-infrared (NIR) fluorescence imaging has been tested to identify the renal tumor boundary after intravenous injection of indocyanine green (ICG), hundreds of clinical cases show that the rate of positive surgical margin has not been reduced because ICG can only visualize the normal kidney tissues and is not able to selectively accumulate in kidney cancer cells. While nearly 40 new fluorescent agents are being evaluated in the clinics for fluorescence-guided cancer surgery, only 2 of them can target and hyper-fluorescently image a subgroup of clear cell renal cell carcinoma (ccRCC) (~50% of all cases) through ligand-receptor interactions and these two new probes fail to target papillary RCC (pRCC), the one with higher recurrence rate, and other types of ccRCC. In addition, the complexity in the probe design significantly increases the manufacture cost, >100 times higher than that of ICG. The goal of ClearNano Inc. is to commercialize a safe, renal-tubule-clearable, tumor targeting NIR fluorescent agent, named “ClearICG” for intraoperative, hyper-fluorescence imaging of kidney cancer including both ccRCC and pRCC. The success of this project will advance the precision of partial nephrectomy for kidney cancer so that oncological and renal functional outcomes can be simultaneously improved while overall medical expense is significantly reduced (~20%). Partial nephrectomy will be the entry market for ClearICG, and its merits over ICG in the long blood retention and tumor targeting will allow it to further replace ICG in other ICG-assisted fluorescence-guided surgeries that require repeated injections and higher image contrast (expanded market).