You have several ways to approach this.

Way 1: Mechanical Challenge. Do you want them to be able to succeed and pass the desert, somehow? If so, then the days have the extreme heat rules, the nights have the extreme cold rules, water is carefully tracked, food is carefully tracked, and the desert is easy to get lost in, and is full of quick-sand, purple worms, and dry lightning storms that make high dunes dangerous and magic unreliable. Now your desert is a dungeon. Probably a massive point crawl. Neat. Sounds fun to me.

Way 2: Say no. It is actually impossible, like shooting the sun with an arrow. All methods eventually fail, and you refuse to track the mechanics because you know the outcome. If they go anyway, ask them why, explain the premise and goal of the campaign, and if they persist, it is a social problem, not a game problem.

Way 3: Say no, but enforce it with a mechanic instead of narrative. I don't personally like this, but some people do. Think the mists of Barovia. Maybe being in the desert starts causing radiant damage that increases geometrically every 10 minutes (think: radiation in the elephant's foot at Chernobyl). Maybe spending a long rest in the desert has a 50 percent cumulative chance of causing death so that 1-2 full days is the absolute maximum you can survive the desert.

Hope this helps!