Microchannel heat sinks and heat exchangers are widely used in the cooling of electronic systems. However, it is still important to enhance the heat transfer in the microchannel so that the intense heat generated can be removed. Vortex generators (VGs) create secondary flow s tructures i n t he fl ow, in creasing th e flu id mix ing, thi nning the the rmal boundary layer, and ultimately boosting heat transfer. Here, we have controlled the flow structure and improved the heat transfer with the lowest possible pressure loss by placing VGs of different sizes, numbers, and angles of attack in a microchannel. The improvement in heat transfer is accelerated as vortex intensity increases. The angle of attack has a significant impact on vortex formation lengths, which reach high dimensions around 90°. Furthermore, increasing the VG length significantly increases the vortex formation lengths. The number of VG pairs
has a significant impact on heat transfer and pressure losses. As the number of VG pairs increases, so does the area occupied by the secondary flow regions in the microchannel, increasing the fluid mixture and boosting heat transfer. The highest enhancement in heat transfer using VGs is obtained at around 230%, while the corresponding increase in pressure loss is 950%. According to the JF factor which we consider a performance evaluation criteria, the best result is around 1.38. The G enetic Aggregation Response Surface Methodology has been applied to numerical results. The related method i s realized t o produce results that are consistent with the numerical results within a ±5% error interval. All the input parameters considered in the sensitivity analysis have an impact of at least 10% on the output parameters.