The Transiting Exoplanet Survey Satellite, or TESS, was scheduled to launch Monday at 6:32 pm (22:32 GMT) atop a SpaceX Falcon 9 rocket from Cape Canaveral, Florida.
Its main goal over the next two years is to scan more than 200,000 of the brightest stars for signs of planets circling them and causing a dip in brightness known as a transit.
NASA predicts that TESS will discover 20,000 exoplanets - or planets outside the solar system - including more than 50 Earth-sized planets and up to 500 planets less than twice the size of Earth.
"They are going to be orbiting the nearest, brightest stars," Elisa Quintana, TESS scientist at NASA's Goddard Spaceflight Center, told reporters on Sunday.
"We might even find planets that orbit stars that we can even see with the naked eye," she added.
"So in the next few years we might even be able to walk outside and point at a star and know that it has a planet. This is the future."
Just a couple of decades ago, the notion of finding habitable planets - or any planets at all - was a mere fantasy, said Paul Hertz, astrophysics division director at NASA.
"Humans have wondered forever whether we were alone in the universe, and until 25 years ago the only planets we knew about were the eight in our own solar system," he told reporters on the eve of the TESS launch.
"But since then, we have found thousands of planets orbiting other stars and we think all the stars in our galaxy must have their own family of planets."
TESS is designed as a follow-on to the US space agency's Kepler spacecraft, which was the first of its kind and launched in 2009. The aging spacecraft is currently low on fuel and near the end of its life.