Background Amidst the growing concern over methamphetamine's ophthalmic sequelae, our study focuses on methamphetamine associated keratitis-induced corneal perforation, a significant but underreported complication of methamphetamine use. Three primary mechanisms have been suspected as the link between methamphetamine use and corneal ulcer formation. Firstly, methamphetamine promotes vasoconstriction which in turn leads to corneal stromal neovascularization. Additionally, methamphetamine can cause neurotrophic keratitis which elevates patients’ pain threshold, potentially delaying care. Methamphetamine users also experience hyper-fixation on foreign body sensations which may result in or worsen epithelial defects due to continued physical irritation of the eye. This retrospective chart review aims to illuminate the correlation between methamphetamine use and the development of corneal ulcer perforation treated with therapeutic penetrating keratoplasty (PKP). Methods We evaluated 8 patients with a documented history of methamphetamine use who developed corneal ulcers which perforated and subsequently underwent PKP at Loma Linda University Health. The study assessed post-operative outcomes, including best-corrected visual acuity (BCVA), complications, graft survival, and follow-up duration. Furthermore, concomitant drug use and associated microbial infections were also examined. Results Our findings underscore the critical impact of methamphetamine use on ocular health, specifically highlighting risk of keratitis leading to corneal perforations. Post-operative outcomes reveal no significant BCVA improvement (p = 0.8323) and poor graft survival rates with an average graft survival time of less than one year. Additionally, the majority of patients had a challenging clinical course with 71.4% of patients demonstrating inconsistent follow-up and 66.7% of patients with at least 6-months of follow-up data experiencing graft failure within one year of their PKP. More than 50% of patients presented with a significant post-operative complication, including corneal edema, epithelial defects, and corneal neovascularization. Conclusion Methamphetamine-induced keratitis presents unique clinical challenges, including a risk for corneal perforation and subsequent need for a therapeutic PKP. Our study highlights the importance of recognizing methamphetamine use as a significant risk factor for severe ocular complications and advocating for early detection and multidisciplinary management to optimize outcomes. The findings call for increased awareness and research into targeted interventions that can reduce the adverse ophthalmic effects of methamphetamine abuse.