Patent foramen ovale (PFO) is implicated in cryptogenic stroke and other clinical syndromes, with transcatheter closure demonstrating superiority over medical therapy in selected patients. Most closure devices are composed of nitinol, a nickel–titanium alloy, raising concerns in individuals with nickel hypersensitivity, one of the most prevalent contact allergies worldwide. Although typically manifesting as localized dermatitis, nickel allergy has been associated with systemic reactions after device implantation, including chest pain, palpitations, migraines, dyspnea, and cutaneous eruptions. Recent evidence indicates that nickel-sensitive patients experience a significantly higher incidence of post-procedural device-related symptoms. Nevertheless, severe reactions remain rare, and the benefits of PFO closure generally outweigh the risks. The predictive value of pre-implantation patch testing remains uncertain, and the lack of nickel-free alternatives constrains device selection. Management strategies are empirical, relying on symptomatic treatment with corticosteroids, antihistamines, or device explantation in refractory cases. Future research should focus on elucidating the pathophysiology of nickel-induced hypersensitivity in cardiovascular implants, improving diagnostic algorithms, and developing biocompatible, nickel-free devices. A multidisciplinary approach involving cardiologists, dermatologists, and allergists is essential to optimize outcomes in this complex subset of patients.