The departure presents what may be the only opportunity to take pictures NASA and many space fans covet of the shuttle, on the eve of its retirement, parked at the $100 billion outpost that is its greatest legacy.
"Hopefully those pictures will show up in textbooks for years to come," said Kenny Todd, NASA's station manager for operations and integration.
Around 5:30 p.m., a Soyuz spacecraft piloted by Russian cosmonaut Dmitry Kondratyev and carrying a NASA astronaut and an Italian astronaut will undock from a port 50 feet from Endeavour and back away to a distance of about 650 feet.
The station then will rotate 130 degrees in an unusual sideways pose that offers a good view of the station, Endeavour, and two cargo ships flown by Russia and Europe.
Italian astronaut Paolo Nespoli will climb temporarily into the windowed Soyuz module — a part of the craft that burns up during re-entry — and begin taking pictures and video of the shuttle and station floating 220 miles above the planet.
Nespoli will have about five minutes to take in the unique view before Soyuz thrusters fire to separate the spacecraft from the station and put Kondratyev, Nespoli and American Cady Coleman en route to a landing in Kazakhstan late Monday night.
It sounds simple enough, but the whole process involves risks that took years to gain acceptance.
"There's been a lot of work by a whole lot of teams to make sure this is really a good thing to be doing, but folks are very comfortable with the plan," Courtenay McMillan, a station flight director, said of the photo opportunity.
"Now, instead of a unique configuration, we have more of what I term more of a unique opportunity," Todd said since not every vehicle would be represented in the picture.
The opportunity arose when shuttle and station program leaders approved what is known as "dual docked operations."
In the past, vehicles coming and going from the station were conflicts for a shuttle mission to avoid.
Another showstopper could be coordinating shuttle and Soyuz crew schedules so each gets enough rest and can execute their separate missions without interference.
In this case, engineers determined there was acceptable rocket fuel plume risk , and the schedules could be managed.
But the photo opportunity presented additional challenges.
The Soyuz will back away much like it always does, but at a slightly higher angle to make sure the sun doesn't blind Kondratyev while he manually keeps the spacecraft hovering behind the station for an extended period.
The station had to figure out a pose that ensured good lighting, and flying in any new position, even for half an orbit, requires verification that systems won't be exposed to harmful temperatures.
The photo orientation is "different enough from what we usually fly that it is outside what we know about, so folks had to go off and do the math and figure out what the problems would be," McMillan said.
After taking the pictures, Nespoli will return to his seat in the crew module and seal the hatch. The crew module separates from two others and is the only part of the ship that survives atmospheric re-entry.
But the Soyuz won't be able to immediately return to its port if there is trouble sealing the hatch, which normally is closed prior to undocking. The maneuver hasn't been studied enough to know it can be done safely.
Managers say a hatch problem is highly unlikely, the Soyuz has backup landing opportunities through Tuesday and managers would come up with a solution if necessary.
"We would get there," said Derek Hassmann, the lead flight director for Endeavour's visit to the station.
Plans continue for another round of photos to be taken during the final shuttle flight. But that could be dropped if Monday's operation produces the desired imagery, which could be released within days.
If the effort succeeds, Todd said he hopes the photos give future generations an appreciation for the feat represented by the station, which couldn't have been built without the shuttle.
"So if we're ever to end up in the future somewhere in a book, it would be great to have the space shuttle represented there with us, as well as all the other international partners," he said.