Lenvatinib (LVN) is a potentially effective multiple-targeted receptor tyrosine kinase inhibitor approved for treating hepatocellular carcinoma, metastatic renal cell carcinoma and thyroid cancer. Nonetheless, poor pharmacokinetic properties including poor water solubility and rapid metabolic, complex tumor microenvironment, and drug resistance have impeded its satisfactory therapeutic efficacy. This article comprehensively reviews the uses of nanotechnology in LVN to improve antitumor effects. With the characteristic of high modifiability and loading capacity of the nano-drug delivery system, an active targeting approach, controllable drug release, and biomimetic strategies have been devised to deliver LVN to target tumors in sequence, compensating for the lack of passive targeting. The existing applications and advances of LVN in improving therapeutic efficacy include improving longer-term efficiency, achieving higher efficiency, combination therapy, tracking and diagnosing application and reducing toxicity. Therefore, using multiple strategies combined with photothermal, photodynamic, and immunoregulatory therapies potentially overcomes multidrug resistance, regulates unfavorable tumor microenvironment, and yields higher synergistic antitumor effects. In brief, the nano-LVN delivery system has brought light to the war against cancer while at the same time improving the antitumor effect. More intelligent and multifunctional nanoparticles should be investigated and further converted into clinical applications in the future.