Thermophoretic enrichment of particles has been recognised as an efficient way to concentrate nanovesicles in biomedical studies. Although some experimental and analytical studies have been undertaken to examine the thermophoretic accumulation mechanisms, few studies have been conducted to optimise the device design. This paper presents a detailed parametric study of a thermophoresis enrichment system, which sandwiches a microchamber containing particle/fluid mixture by a glass top, from where an infrared light laser heat source is introduced, and a sapphire bottom, which has a high heat conductivity to prevent overheating. The influences of the laser spot radius, laser attenuation rate, nanoparticle size and laser power are investigated. The radius of the final nanoparticle distribution is found to be approximately 1.25 times the laser spot radius. A reduction in the laser attenuation length leads to a reduction of the time taken by the nanoparticles to reach the steady state, but an enlarged final area over which nanoparticles are concentrated. There exists an optimum range of the attenuation length, depending on the size of the target area. We have also determined the threshold particle size, which decides whether the particle motion is convection-dominated or thermophoresis-dominated. Furthermore, an increase in the laser power reduces the accumulation time. These findings provide guidelines of the design of enrichment systems.