Various systemic and topical medications can induce ocular and periocular cutaneous adverse effects (AEs), ranging from mild to severe. These AEs may lead to ocular surface (OS) damage and, in some cases, life-threatening complications. Drug-induced ocular adverse reactions are generally classified into two primary categories: toxic reactions and/or allergic hypersensitivity reactions, which can be IgE or non-IgE-mediated. Systemic antibiotics, antivirals, and anticonvulsants can trigger adverse reactions that may involve the OS. Drugs like antihistamines, beta-blockers, antipsychotics, antidepressants, and isotretinoin are linked to dry eye disease. Topical treatments—including antibiotics, antiglaucoma medications, preservatives, contact lens solutions, and cosmetics—may elicit allergic or toxic ocular diseases. Recent evidence implicates ocular surface AEs in patients undergoing biological treatments for oncological diseases and atopic dermatitis. Epidermal growth factor receptor inhibitors, used in the treatment of several cancers, have been associated with conjunctivitis, meibomitis, dry eye, periocular skin changes, and trichomegaly. Similarly, dupilumab, the first biologic approved for treating moderate-to-severe atopic dermatitis, has also been linked to OS disease with blepharoconjunctivitis. This position paper provides a comprehensive overview of the clinical presentations, diagnostic approaches, and treatment strategies for drug-induced ocular AEs, integrating the latest literature and clinical guidelines.