The crew of mission "Crew-3" will spend six months on the orbital outpost, conducting research in areas including material sciences, health, and botany, to help inform future deep space exploration and benefit life on Earth.
Americans Raja Chari, Tom Marshburn, and Kayla Barron as well as German Matthias Maurer of the European Space Agency (ESA) will launch aboard a Crew Dragon spacecraft named "Endurance," fixed atop a Falcon 9 rocket at 2:21 am (0621 GMT) from the Kennedy Space Center in Florida.
"Last night we got to go see Endurance in the hangar as they got ready to roll it out to the pad, and actually put our hands on the Dragon, which is a pretty special experience," Chari, a US Air Force colonel who is commanding the mission, said at a press conference on Wednesday.
Of the four, only Marshburn has gone to space before. The medical doctor flew aboard a Space Shuttle in 2009 and a Russian Soyuz spacecraft in a mission from 2012-13.
Barron, who along with Chari was selected for the NASA astronaut corps in 2017, the most recent recruitment, previously served as a submarine warfare officer for the Navy, and told reporters she saw many parallels between that experience and going to space.
The pair are also in the mix for NASA's Artemis missions to return humans to the Moon later this decade.
Maurer, a materials science engineer, will become the 12th German to go to space and will join fellow ESA astronaut Thomas Pesquet of France on the ISS, an overlap that will likely last a few days before the Frenchman returns to Earth with the rest of his Crew-2 colleagues.
Following a 22-hour voyage, Endurance will autonomously dock with the space station at 12:10 am Monday (0410 GMT).
More about: NASA
