In this Letter, we propose a locally optimized Stokes polarimetry. Focusing on the effect on polarization measurements by Poisson noise, the studies establish a new, to the best of our knowledge, optimization function combining the equally weighted variance with the condition number. This method considers both the stability and the precision of polarization measurements; by trading an increase in the condition number by 2.48%, we realize a decrease in equal-weighted variance by 19.1% near the north pole. The advantages of this local optimization method are demonstrated based on Monte Carlo (MC) simulations and experiments of continuous polarization state modulation. Finally, an imaging demonstration using a 4 µm pathological section implies the potential of this new local optimization method in improving polarization measurements and applying it to more biomedical research.