The intersection of the Mississippi and Missouri rivers is where St. Louis, Missouri's second-largest city, is located. The bi-state metropolitan region, including Illinois, was predicted to have a population of about 2.8 million in 2020, making it the largest in Missouri and the second-largest in Illinois. The city proper had a population of 301,578.

St. Louis is currently the home of 11% of the population in the metropolitan area in the twenty-first century. While the city experienced a slight increase in the early 2000s, it saw a decline in population from 2000 to 2010. The largest Bosnian community outside of Bosnia and Herzegovina still immigrates to the city, attracting Latin Americans primarily from Mexico and Vietnamese. The St. Louis metropolitan area, situated to the south, may have a hot-summer humid continental climate (Dfa), demonstrating the influence of the urban heat island in the region. St. Louis' urban area has a humid subtropical climate with hot, humid summers and cold winters that can range from cool to freezing, affected by both the hot, humid tropical air from the Gulf of Mexico and the cold Northern air.

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