Herpes zoster which is the reactivation of varicella-zoster virus, a pathogenic human alpha-herpes virus, following primary infection or chicken pox, is known to occur especially in advanced age and in the immunocompromised among other predisposing factors. COVID-19 vaccination-induced immunomodulation is a novel scenario, hypothesized to be a result of shifting of T-lymphocyte population towards vaccine-induced naïve CD8+ subset, offsetting the balance of varicella-zoster virus responsive T-helper cells, thereby defecting the cell-mediated immunity which suppresses the latent varicella-zoster virus. The exact mechanism, however, is still elusive. Herein, we discuss a case of reactivation of varicella-zoster virus following BNT162b2 mRNA COVID-19 vaccine in an elderly female on oral medication for long-term diabetes and hypertension with good control who has undergone local radiotherapy for an underlying adenocarcinoma of rectum awaiting surgical resection, highlighting the key features of pathogenesis of the disease in relation to COVID-19 vaccination with a pertinent survey of the literature. This case report highlights the importance of differentiating vaccine-related cutaneous reactions with clinically more significant adverse events, early specific therapy thus preventing poorer acute and chronic outcomes.