Pilot Bertrand Piccard is at the controls one final time.
His flight ought to be fairly straightforward, although his team has some concerns about how the heat in the Middle East may affect the plane.
Mr Piccard is likely to have to spend a lot of time at high altitude on oxygen to get above the thermals and the turbulence they induce.
The warmer, thinner air above the Saudi desert also means Solar Impulse`s motors will have to work harder to propel the vehicle forward.
This will require careful management of the energy reserves in the plane`s lithium polymer batteries, to be sure they can sustain the aircraft through the night hours.
"We thought it was going to be an easy flight because it`s always good weather between Egypt and Abu Dhabi across Saudi. But actually, it`s extremely difficult to find a good strategy," Mr Piccard told BBC News.
Solar Impulse has covered some 30,000km in its quest to become the first plane to circle the world using no fuel, just the energy from the Sun.
The Cairo-Abu Dhabi flight marks the 17th and final segment in the journey, which has included crossings of the Pacific and Atlantic oceans.
Mr Piccard has alternated pilot duties with his friend and business partner Andre Borschberg.
The pair had hoped to complete the challenge last year but progress was not quite swift enough to get the best of the weather in the Northern Hemisphere`s summer.
And when battery damage was sustained on an epic five-day, five-night passage over the western Pacific in June/July 2015, the decision was taken to ground the effort for 10 months.
For Mr Piccard, landing back in Abu Dhabi will represent the closure of a 17-year undertaking to prove that a solar plane could circumnavigate the globe.
The idea was born when he made the first, non-stop, round-the-world flight in a balloon in 1999.
His Breitling Orbiter 3 envelope only just made it, landing in the Egyptian desert with virtually no reserves left of the propane gas it had been using in burners to stay aloft.
Mr Piccard said he vowed then that "there had to be another way".
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