Saint Louis, MO is located at the eastern edge of Missouri, bordering Illinois along the Mississippi River.

As a result, several major cities are distributed within a 50-mile radius across both Missouri and Illinois. These areas are frequently visited by Saint Louis residents for various reasons, including living, shopping, tourism, and business.

The closest major city on the Missouri side is St. Charles, MO. Located about 25 miles from downtown Saint Louis, St. Charles is a historic city situated along the Missouri River, famous as the starting point of the Lewis and Clark Expedition. The Historic Main Street, a preservation area, is lined with independent shops and restaurants, making it a popular weekend getaway. The population is around 70,000, and it is part of the Saint Louis metropolitan area (MSA).

Florissant, MO is located about 15 miles north of Saint Louis and is a residential city with a population of approximately 50,000. It is one of the oldest cities in Missouri, retaining a history from the French colonial era. Chesterfield, MO is an affluent suburban city located about 20 miles west of Saint Louis, home to the upscale shopping center Chesterfield Valley and various corporate headquarters. Other satellite cities adjacent to Saint Louis include Olivette, Clayton, and Kirkwood, with Clayton serving as the administrative capital of Saint Louis County.

Crossing the river into Illinois, East St. Louis, IL is immediately adjacent and is known for its long-standing economic challenges. Belleville, IL is an Illinois city located about 15 miles from Saint Louis and serves as the administrative center of St. Clair County. Edwardsville, IL is a growing city in southern Illinois, home to the Southern Illinois University Edwardsville campus (SIUE). Collinsville, IL is located about 12 miles from Saint Louis and is known for its unique tourist attraction, the World's Largest Catsup Bottle. The areas around O'Fallon, IL and Scott Air Force Base are also included in the Saint Louis metropolitan area.

Further out from the 50-mile radius, Springfield, IL is located about 100 miles away, which is outside the radius, but other cities within 50 miles include Wentzville, MO (about 35 miles), Warrensburg, and the distant Ferguson, MO. Ferguson gained national attention due to a police shooting incident in 2014 and is located in the northern part of Saint Louis. The metropolitan area centered around Saint Louis spans both Missouri and Illinois, making it important to consider taxes, school districts, and commuting distances when choosing a place to live.