This perspective article delineates the significant role of hypoxic pockets-localized, transient reductions in cerebral oxygenation-and their implications for stroke neuroprotection strategies. It posits that preconditioning and postconditioning, through interventions like isoflurane, exercise, remote limb ischemic conditioning, can mitigate these hypoxic pockets, potentially protecting the brain against ischemic events. These strategies exploit the brain's intrinsic adaptive capabilities to resist ischemic damage, underscoring a novel avenue for enhancing recovery and prevention efforts. The study emphasizes the need for further exploration into optimizing these interventions to harness their full potential in combating stroke's debilitating effects, marking a pivotal shift towards targeted neuroprotective measures focused on cerebral microenvironmental optimization.