Vegas to Reno
 

I've never done the drive before but will be doing it soon, planning to overnight perhaps in Hawthorne.

Are there any sections that would be a tough drive ? Is winter weather likely to be a problem anywhere along the route ?

I hate that drive. 400 miles of mostly two lane road with limited passing opportunities.

I've never driven it during inclement weather but could see issues in northern NV if a winter storm is passing through (remember to take survival items, and consider delaying if the weather looks questionable). Remember that in a lot of the drive you're miles from nowhere.

If the weather is good then it's not difficult, just annoying and looooong.

+1, and lots of cell phone dead spots too so don't rely on that.

Also plan your gas stops. Beatty, Tonopah, Hawthore, and Fallon are about the only towns with reasonable services along the trip.

What route are thinking of taking? The shortest route, US 95 to US 50 to I-80, is miles and miles of nothing. I wouldn't do it for the scenery.

Winter weather isn't a huge issue. You're going from lower desert (2000' elev) in the south to high desert (4500' elev) in the north. Snow falls in the high desert but usually not too much since it's still relatively dry.

Alternatively you could veer farther west, say going through Death Valley to US-395 in California. This route is full of interesting things to see and do. But it's longer, and the chance of wintry weather causing delays and/or chain restrictions is much higher as US 395 crosses well over 6000' elevation in northern California/Nevada.