Aims Perineural spread (PNS) of cutaneous squamous cell carcinoma (cSCC) is a challenging entity with significant morbidity and poor survival. Australia has the world's highest burden, with cSCC the most common malignancy to cause PNS of the head and neck. This review evaluates the evidence for multidisciplinary management, integrating advances in imaging, skull base surgery (SBS), radiotherapy (RT), and immunotherapy. Methodology This review draws on institutional data from a high-volume quaternary skull base centre in Queensland, Australia. Epidemiology, diagnostic imaging, surgical approaches, RT dose-framing strategies, treatment outcomes and patterns of failure were systematically evaluated. The Royal Brisbane and Women's Hospital (RBWH) sub-classification of Williams zone 2 disease (2a/2b) and its clinical implications are described. Results SBS and postoperative IMRT achieves 5-year relapse-free survival of 60–65%, disease-specific survival of 68–77%, and overall survival of 58–67% — representing a 20–25% improvement over historical RT-alone series. Williams zone is the strongest prognostic factor. Local skin/dermal failure dominates recurrence patterns (~60%), highlighting under-treatment of the index site. Wider surgical margins, dermatomal and bolus to cutaneous fields are recommended. Anti-PD-1 checkpoint inhibitors show response rates of 69–83% in retrospective PNS-specific cohorts. The C-POST trial showed significant disease-free survival benefit with adjuvant cemiplimab, while neoadjuvant studies signal potential for treatment de-escalation. Conclusion Optimal management of cSCC with PNS requires expert multidisciplinary care combining 3T MRI, SBS, and IMRT. Addressing the skin/dermal failure problem demands greater surgical and RT margins. Immunotherapy is rapidly reshaping the treatment paradigm, particularly for high-morbidity resections and unresectable zone 3 disease, but even in classically resectable disease with a high degree of morbidity.