The methods for the optimization of the magnetoresistive (MR) sensors are to reduce sources of noises, to increase the signal, and to understand the involved fundamental limitations. The high-performance MR sensors result from important magnetic tunnel junction (MTJ) properties, such as tunneling magnetoresistance ratio (TMR), coercivity (Hc), exchange coupling field (He), domain structures, and noise properties as well as the external magnetic flux concentrators. All these parameters are sensitively controlled by the magnetic nanostructures, which can be tuned by varying junction free layer nanostructures, geometry, and magnetic annealing process etc. In this paper, we discuss some of efforts that an optimized magnetic sensor with a sensitivity as high as 5,146 %/mT. This sensitivity is currently the highest among all MR-type sensors that have been reported. The estimated noise of our magnetoresistive sensor is 47 pT/Hz1/2 at 1 Hz. This magnetoresistance sensor dissipates only 100 μW of power while operating under an applied voltage of 1 V at room temperature.