The division between the two municipalities follows the course of Gardiners Creek, which is a tributary of the Yarra River. A tributary of Gardiners Creek running north through the suburb, Back Creek, has largely been turned into a drain. Also roughly following the course of Gardiners Creek is the Monash Freeway, and the Glen Waverley train line.

Two train stations on the Glen Waverley line, Gardiner and Glen Iris, lie within the suburb. Passing through the eastern part of Glen Iris is the Alamein train line, with Burwood station within Glen Iris. (Glen Iris did not originally go this far east, and this station and its surrounds were once in the suburb of Burwood). Residents are also served by the numbers 6 and 72 tram routes, as well as the numbers 612 and 734 bus routes.

Melbourne's demographic centre lies within Glen Iris, as the city's urban sprawl spreads further to the east of the CBD than to the west.

To the east of Glen Iris lies Malvern, to the north is Camberwell and Hawthorn East, the west, Burwood, and the south Malvern East and Ashburton.