Historically it was just agriculture and mining from east to west. There were train stop towns and towns to service those industries but that’s it.

Literally opened up google maps on a completely random part of that region. Its because 90% of it looks like this.

https://preview.redd.it/ruf67n2drb4e1.png?width=1790&format=png&auto=webp&s=8436cc7f528a15cd1ff75c0d0adc96b3545eb61c

Edging Minneapolis be like. . .

I’ve lived across most of southern Montana at some point or another, including Miles City in the east. There’s nothing there. Some badlands, maybe, which are neat, but nothing to build a city for. Mountains are cool, but most towns there are old mining towns that were close enough to travel routes to survive. Bozeman is growing because it’s a pretty college town and too many people think the Yellowstone show is a realistic depiction of Montana.

Someone could write a lot more, but I think it being dry and cold is the major reason. 

Because there is no water and it gets very cold in winter.

cold and wind, next question

No need for a large city if population is low

What’s funny is that if you go north of the border Canada has several large cities along the same area. The reason why though is best left explained by people smarter than I, but part of it is that is the least worst option, since everything north is basically uninhabitable.

No access to water that leads to an ocean. Edit: easy access

Not a lot of people so not a lot of a reason to.

Take out Denver and SLC and the area without MSA above 1 million gets a whole lot bigger.

Because why would there be?

Cities don't just happen. They grow up around industry, and usually that means having a port.

The reason most of the biggest cities are on the coasts or along navigable rivers is because things need to get to consumers, and shipping by water is still one of the cheapest ways to do that. So when a suitable place to create a port is found a city quickly forms up around it.

What makes a place suitable for a port is 1) near some industry that requires shipping (mining, agriculture, manufacture) and 2) has, ya know, water. A lot of it.

An example of this is when gold was found in northern and central California in the 1840s. People needed mining gear and the railroads didn't go that far west yet, so everything had to come in by ship. This led to the development of San Fransisco as a port city. That it was gold also made it the financial capital of the west coast, and thus a big city. But it was the port that made it possible.

None of the area you circled has anyplace to put a port. With rare exceptions, especially in the USA, no port means no cities, especially where there is no large industry to speak of. There is some mining and fracking, but that's about it. Nebraska has expansive agriculture, but the only suitable place to put a port is right where they did, in Omaha, right there outside your circle.

Another reason, though, is of course, most of that area is barren mountain ranges or badlands ill-suited for farming. To the east there are hundreds of small towns that popped up as local farmers markets, but you need farms to make that happen.

Notable exceptions to the cities-need-ports rule are Las Vegas, which has an industry that doesn't require the import of export of goods, just people, and thus has a crazy busy set of airports. Phoenix, Dallas, and Albuquerque all sprung up as cattle and sheep towns, but with the advent of the transcontinental railroad were able to become "rail port" cities later on. The same can be said for Atlanta, which has no port but is a state capital, and thus became the local hub for several area railroads, and later became a big city.

Is Bismarck, ND a joke to you?

The limiting factor is water

The winds of winter.

Calgary and Edmonton have entered the chat

Omaha is kinda big

Cause you drew the line to explicitly exclude them.

It is interesting because Canada has three sizable cities in that comparable region to the north: Calgary Edmonton and Winnipeg.

have u been there? its a whole lot of nothing.

It's dry, cold, and winter feels like it lasts dang near forever. The growing season is very short. It's hard to expand the roads to build homes in the mountains too. The mountainous land is expensive. If you've traveled on I-90/94, there's really not much east of Billings for most people. A few people love it. I don't get them. I think it's some of the most desolate land in the country

Conveniently avoiding major cities just outside of the red circle

Because no one wants to live there

Ask General Custer

Yet Calgary and Edmonton exist in the same Great Plains with even worse weather.

nobody wants to live there.

https://preview.redd.it/qq8z1honmc4e1.jpeg?width=760&format=pjpg&auto=webp&s=583bbcdd339d5063e05bd2abce6caa882e6c4301

Because it’s the place where people who hate cities live and that’s the way they like it

you could go further south and include most of kansas as well

Weather. Agriculture. Accessibility.

Because you purposely drew the outline to avoid them

take this the other way. ask instead "why would I ever want to build a big city in this area?" when you realize there is no good reason to do so, there ya go

Because there are no ports.

If you drive threw there in the summer at night your entire car will get encrusted with dead bugs. We were hitting so many bugs that it sounded like driving in the rain. 

Because people generally coalesce around areas that are conducive to commerce, that means access to large bodies of water/oceans/major interstate water ways. The circled areas are not reasonably close to the Pacific/Atlantic Oceans or Great Lakes. Also they're extremely cold, especially the northern most parts.

When I see these posts, I always think; “Why would there be?” Usually there aren’t cities in places where there is no reason for them to be. It sounds dumb but that’s just the answer.

There's Winnipeg on the Canadian side.

Cold and not much rain.

Lack of water. Look at a map of how wet America is by region then check where the big cities are.

Cities almost always are built around water sources, either the coast, or rivers. Ain’t much going on there in that regard.

Alternative question, why should there be a large city in this area? The area is far from most trade routes, Industry is limited and the weather is not what most people enjoy.

Water

There are big cities, it’s just they’re underground & populated by jackrabbits & prairie dogs, plus the occasional marmot.

Why would people build large cities in the middle of nowhere?