"There's still a certain amount of disbelief that it's really her final launch," launch director Mike Leinbach said at a news conference. "It's difficult to accept emotionally. But rationally, we all know it's coming to an end, and we need to get on with it."
For its grand finale, Discovery and a crew of six will head to the International Space Station with a load of equipment, including a humanoid robot.
It will be the 39th flight for Discovery over 26 years. A museum will be its final destination; the Smithsonian Institution gets first pick.
As of Monday, the forecast called for a 70 percent chance of favorable weather for the 3:52 p.m. launch. But shuttle weather officer Kathy Winters cautioned that storms were expected Thursday, and Wednesday's outlook could worsen if the bad weather arrives sooner than anticipated.
NASA has until Sunday -- possibly as late as Monday -- to launch Discovery. If the oldest surviving space shuttle isn't flying by then, it will remain grounded until at least December.
Discovery was supposed to blast off Monday, but a pair of gas leaks in the rocketship forced a two-day postponement.
Discovery's last journey puts NASA a step closer to wrapping up its shuttle program and shifting its focus to rockets and spacecraft capable of carrying humans to asteroids and Mars. Only one other shuttle mission remains on the official lineup, by shuttle Endeavour next February and March.
NASA officials would like an extra flight in mid-2011, but lawmakers have yet to fund it. Plans for NASA's shuttle replacements also are in flux in Washington, with no firm date on when they might fly or what they might be.
Everyone at NASA would prefer having a new rocketship ready to fly before giving up the old.
"But the realities are that NASA is on a fixed budget, just like most American families, and without a big infusion of cash, we can only do a couple of things at a time," said Mike Moses, chairman of the prelaunch mission management team.