Tumor necrosis factor-α (TNF-α) inhibitors, such as adalimumab, are widely used for the treatment of various inflammatory diseases, including psoriasis. Injection site reactions (ISRs) are common side effects, typically mild and self-limiting. Nevertheless, in some cases, ISRs may persist or evolve into more severe hypersensitivity reactions, requiring discontinuation or a change of the therapy. We present the case of a 40-year-old woman with plaque psoriasis who developed progressive ISRs and recall reactions during adalimumab therapy. Allergological diagnostics confirmed a delayed-type hypersensitivity reaction. Transitioning to an IL-12/IL-23 inhibitor resulted in clinical improvement, highlighting the importance of allergological testing and alternative biologic therapies.