It connects southern Tompkinsville in the north to northern Arrochar in the south, passing through the Fort Wadsworth, Rosebank, Shore Acres, Clifton, and Stapleton neighborhoods.

[1] Between Hylan Boulevard and the Staten Island Railway overpass, Tompkins Avenue becomes one of Rosebank's two commercial districts (the other being along Bay Street).

Landmarks between Vanderbilt Avenue and Broad Street include the St. Elizabeth Ann Healthcare and Rehabilitation Center, a nursing home opened in 1990 that is run by the Sisters of Charity, P.S.

[11] The Grant City-bound S51 runs on a small portion from School Road to Lily Pond Avenue.

[13] The Fort Wadsworth Station at one time did exist at the foot of Tompkins Avenue, near School Road along the Staten Island Rapid Transit's former South Beach line.