Midway between New York and Miami, the Grand Strand isn't connected directly to any interstate highways but is within an hour's drive of Interstate 95, Interstate 20, Interstate 26, and Interstate 40 via Route 22 (Veterans Highway), U.S. 501, and the newer Route 31 (Carolina Bays Parkway). U.S. 17 Bypass and U.S. 17 Business are the major north–south coastal routes through the Strand.

In summer, to bypass incoming southbound traffic jams on U.S. 501, take Interstate 95 to Interstate 40 to U.S. 17 (at Wilmington) to Route 31, which connects to Myrtle Beach via Route 544 or the tail end of U.S. 501.