Nanoparticulate drug carriers exploit the enhanced permeability of tumor vasculature to achieve selective delivery of chemotherapeutic drugs. For this purpose, nanoparticles (NPs) need to circulate with a long half‐life, enter tumors via the permeable vasculature and stay in tumors via favorable interactions with tumor cells. To fulfill these requirements, albumin‐coated nanocrystal formulation of paclitaxel (PTX), Cim‐F‐alb, featuring high drug loading content, physical stability in serum, and surface‐bound albumin in its native conformation is prepared. The pharmacokinetic and biodistribution (PK/BD) profiles of Cim‐F‐alb in a mouse model of B16F10 melanoma show that Cim‐F‐alb exhibits a longer plasma half‐life and a greater PTX deposition in tumors than Abraxane by ≈1.5 and ≈4.6 fold, respectively. Biolayer interferometry analysis indicates that Cim‐F‐alb has less interaction with serum proteins than nanocrystals lacking albumin coating, indicating the protective effect of the surface‐bound albumin against opsonization in the initial deposition phase. With the advantageous PK/BD profiles, Cim‐F‐alb shows greater and longer‐lasting anticancer efficacy than Abraxane at the equivalent dose. This study demonstrates the significance of controlling circulation stability and surface property of NPs in efficient drug delivery to tumors and enhanced anticancer efficacy.