Substance use disorders, including methamphetamine use disorder, are prevalent, causing extensive morbidity and death. Despite advances in evidence-based treatments for methamphetamine use disorder, many patients do not respond to these interventions, and new approaches are needed. Deep brain stimulation (DBS) involves the surgical implantation of a device to modulate nervous system function and has proven efficacy in the management of movement disorders. Recent studies of DBS for the management of substance use disorders have shown promise, and the authors of this review are currently investigating DBS for the treatment of patients with methamphetamine use disorder. However, acute and chronic intoxication with methamphetamine can result in various systemic abnormalities and medical comorbid conditions, presenting challenges for the neurosurgeon, the anesthesiologist, and other medical providers. This narrative review aims to provide a comprehensive overview of methamphetamine's systemic effects and associated medical comorbid conditions for clinicians engaged in the perioperative care of this patient population. The systemic effects and related medical comorbid conditions that may complicate the perioperative course of patients with methamphetamine use disorder are presented by organ system. With diligent preoperative planning and perioperative management, patients with methamphetamine use disorder can be successfully treated with DBS surgery. A thorough understanding of these effects and comorbid conditions is crucial for both the prevention and the rapid recognition of perioperative complications, resulting in improved outcomes in this patient population.