The invention generally relates to systems and method for deep learning driven adaptive optics for single molecule localization microscopy. In certain aspects, the invention provides a system comprising: an imaging apparatus configured for conducting single-molecule localization microscopy (SMLM), wherein the imaging apparatus comprises a deformable mirror and a dynamic filter; and a processor operably associated with the imaging apparatus. In certain embodiments, the processor is configured to: monitor individual emission patterns produced via the imaging apparatus from a plurality of different single molecules in a sample; infer shared wavefront distortion for each of the individual emission patterns; provide the shared wavefront distortion for each of the individual emission patterns through the dynamic filter; and operate the deformable mirror to compensate for sample induced aberrations.