Spatial and temporal precisely control of direction and speed is crucial for nanomotors to enable complex operations and applications in microsurgery, drug delivery, isolation of biological targets, and so on. Judicious material design involving Janus nanoparticles has been popular over the past decades, however, precise and customizable modulation of Janus structure with a specific asymmetric ratio for motion control is still challenging. In this study, a universal “interface allocation” strategy is developed for efficient and controllable preparation of Janus mesoporous silica‐coated upconversion nanoparticles (Janus UCNP@mSiO2) with precisely tuned asymmetric ratio to achieve near‐infrared (NIR)‐controlled active mobility for relieving vessel plaque. Mesoporous silica with a thickness of 50 nm is precisely coated onto the nanoparticles’ surface with an optimal coverage ratio of 50% to encapsulate gas propellant. Upon exposure to upconverted blue light, the nanomotors release nitric oxide, facilitating their motion and pathologically improving atherosclerosis through endothelium‐dependent vasodilation. Experimental and theoretical simulation results demonstrate the advantages of NIR‐controlled Janus upconversion nanomotors in atherosclerosis treatment, including enhanced nanoparticle‐transmittance rate (34.83% to 85.57%) and excellent in vivo therapeutic efficacy.