The region includes the Atlanta, Birmingham, Charlotte, Memphis, Nashville, Research Triangle (Raleigh–Durham), Upstate South Carolina (Greenville–Spartanburg–Anderson), and Greensboro–Winston-Salem–High Point metropolitan areas.

According to Georgia Tech, the Piedmont Atlantic represents over 12 percent of the total United States population and covers over 243,000 square miles (630,000 km2) of land.

Studies by Virginia Tech and Georgia Tech identify the 85/20 corridor in the Southeastern United States area as an "emergent" megalopolis including the primary cities of Atlanta, Birmingham, Greenville, Spartanburg, Charlotte, Winston-Salem, Greensboro, Durham, and Raleigh with Atlanta being the largest metropolitan area and Charlotte being the largest city.

The Virginia Tech study proposes a broader definition, which would also include Columbus, Macon, Huntsville, Augusta, Columbia, Knoxville, Chattanooga, the Tri-Cities, Asheville and a number of smaller cities.

Other locales mentioned in the Virginia Tech study remain disconnected from the region's core, separated by dozens of miles of deeply rural areas.

Birmingham boomed after the Civil War as a major industrial center in the Southern United States, the city's economy has diversified into banking, insurance, medicine, publishing, and biotechnology.

Mayors, businesses, and academic professionals have organized the Piedmont Alliance for Quality Growth to help address these problems with sustainable solutions.

With the goal of focusing on the growth of the megaregion, they have called for less competition between cities and metropolitan areas in the same region, and a stronger and more cohesive ability to work together to compete on the global scale.

The major issues facing the Piedmont Atlantic megaregion include conflicts over shared natural resources such as water and problems of transportation infrastructure such as upkeep of roads and railways linking cities.

The Sloss Furnaces National Historic Landmark and the Vulcan statue and museum that overlooks the city and provides views from atop Red Mountain details the industrial history of the area.

Major attractions in the region are the area around Asheville, Great Smoky Mountains National Park (the US's most visited National Park), the Blue Ridge Parkway (the US's other most visited park), Mt Mitchell (the highest mountain in the eastern US), the Appalachian Trail, the Chatooga Wild and Scenic River, the Jocassee Gorges, Grandfather Mountain, the Ocoee River, the Tail of the Dragon, and Pisgah National Forest.