Friday's qualifying will start at midnight and Saturday's race will start at 10pm Nevada time, with the latter potentially running until after midnight if there is a red flag delay and restart.
Records suggest that in mid-November, ambient temperature is likely to dip below 10 degrees Celsius, and it could go as low as five degrees.
Those sorts of numbers will clearly put a premium on getting the tyres into the right window, especially for qualifying laps, at the start, and after safety car restarts.
"It'll just depend on exactly how cold it is," said Mercedes trackside engineering director Andrew Shovlin when asked by Motorsport.com about the challenge.
"Because if the track is down in single figures, that's often a region where you go winter testing.
"You do a run, it's very difficult for the tyres to either get them switched on, or there may be graining and things. And then sometimes you just wait until it warms up a bit. So actually having to sort of race and qualify in those conditions, it will be interesting.
"You just try and identify the risks with the new circuit, work out what your contingencies will be, whether you need any sort of specific car spec to deal with that. And we're going through that at the moment.
"But as I said, if it's at the very cold end of predictions, it's difficult to know how the tyres are going to work."
AlphaTauri chief race engineer Jonathan Eddolls agreed with the comparison with testing.
"The temperatures are going to be probably one of the biggest challenges," he said. "I think we're expecting circa 10C of ambient, so very much like the winter test.
"In many years, we've done winter tests in Barcelona at those sorts of temperatures. So it's not going to be completely new to us.
"But definitely it's quite a step away in terms of where we're going to be operating the current tyres to what we're used to in a normal season."
Haas director of engineering Ayao Komatsu suggested that the weather could actually help his team, which has struggled this year with high tyre temperatures.
"It's a very different temperature window, so we've got to get the tyres to work," he said. "But if I had to choose hot or cold, I'd choose cold conditions at this minute! So hopefully, we can get it to work.
"I think it'll be a big challenge for us, especially our team with the tools we've got in terms of pre-event simulation, more limited compared with let's say Mercedes."