Anal Melanoma (AM) is a rare and aggressive disease lacking standardized treatment protocols. Despite advancements in medical oncology, the 5-year overall survival (OS) remains at 20%. Local surgery (LS) has gained popularity over radical surgery (RS) due to its comparable OS when negative margins are achieved. Neoadjuvant chemotherapy and radiotherapy do not improve margins status, while neoadjuvant immunotherapy (Neo-IT) has not been studied on AM margins status. Patients diagnosed with AM in the National Cancer Database (2011-2021) who received Neo-IT were retrospectively identified and divided into two cohorts based on the surgical approach (LS or RS). In each cohort, patients were matched in a 1:1 ratio to those who did not receive Neo-IT based on age and tumor size. Univariate analyses were performed to compare Neo-IT influence on surgical margins in both cohorts. Thirty patients were included in the LS cohort, with 56.7% of positive margins. Univariate analysis revealed that Neo-IT did not improve surgical margins in LS in AM (p value = 0.713). However, the 22 RS (31.8% positive margins) patient cohort's univariate analysis revealed that Neo-IT significantly improved surgical margins in AM (p value = 0.022). Achieving negative margins is crucial to increase OS in anal melanoma. Neo-IT appears to improve negative surgical margin status in RS for anal melanoma. However, Neo-IT did not improve margins in LS. This opportunity to improve margin suggests a potential to increase the 5-year OS of 20%. Future work is needed to determine the impact to OS and confirm the IT role in LS.