As the vast majority of goods in the United States are moved via highway transportation, the locations of Twin Falls and Jerome right along major highways are seen as beneficial to many businesses. The Twin Falls-Jerome area is served by Interstate 84 as the major east-west route and US Highway 93 as the primary north-south highway access route. US Highway 30 also serves Twin Falls as an additional east-west highway access route and Highway 26 serves the Jerome area as an east-west route.

To the west, I-84 provides direct access to Boise, Portland and Seattle via connection to I-82 and I-90. The primary access to the eastern US is provided by I-84 via the connection with I-15 which in turn connects with I-80 at Salt Lake City. I-80 is one of the major US east-west interstate routes extending from New York to San Francisco. US Highway 93 is the major north-south highway route through the area. From the south US 93 enters Twin Falls County at the Nevada state line traveling north throughout the City of Twin Falls crossing the Snake River Canyon via the Perrine Bridge to connect with I-84 in Jerome County, about three miles north of the Twin Falls city limits. US 93 also connects with I-80 about 120 miles south of Twin Falls at Wells, Nevada.

Locally, the City of Jerome is located roughly 12 miles northwest of Twin Falls. The State Capital in Boise is located about 115 miles northwest and Salt Lake City about 230 miles southeast. Jerome adjoins I-84 with two inter-changes, with the main exit about 2 miles south of the city center. Jerome is also the location of the intersection of US Highway 93 and I-94, about 6 miles to the southeast of Jerome city center and 3 miles north of Twin Falls city limits.

Twin Falls is located 3 miles south of I-84 with one major interchange at US Highway 93 and I-84. Additional interchanges provide secondary access to the interstate system form Twin Falls on the eastern and western side of the city via US 30. New industrial areas and an inter-modal facility being developed on the south and east of town will added to the easy transportation access for local businesses.

Local businesses find that thanks to the interstate availability, their goods/products are only a one day truck route to Oregon, Washington, Utah and Nevada, and just two days to California, Colorado and Arizona.