The ITI follows the route of the famous Iditarod sled-dog race, which starts a week later. The dog-sled race commemorates the 1925 serum run to Nome. The route follows frozen rivers and traditional trails used by the native Athabaskan and Inupiaq peoples. The conditions are weather dependent and it is not unusual for Nome racers to have to push their bikes through deep snow for tens and and even hundreds of miles.
It starts from Knik Lake, north of Anchorage. The first part of the race follows the Skwentna River to Finger Lake, after which the route becomes more technical and challenging to reach Puntilla Lake. After crossing the Alaska Range at Rainy Pass racers cross the Farewell Burn to reach the settlements of Nikolai and then McGrath (the end of the 350 mile race).
After McGrath there is a long desolate stretch through the ghost towns of Ophir and Iditarod before reaching the Yukon River at Anvik. It is a long and cold 120 miles up the Yukon against the prevailing wind, where wind chill temperatures can drop below -50 Fahrenheit.
The race reaches the Berent Sea at Unakleet and then follows the coastline until just after Shaktoolik, where it heads straight across the frozen Norton Bay to Koyuk. From Koyuk the trail runs along the shore and over the Kwiktalik Mountains to Golovnin and then White Mountain. The exposed stretch from White Mountain to Safety often sees strong winds and ground blizzard conditions. From Safety it is a 20 mile run to the finish line at the famous burled arch on Front Street in Nome.