Project scientist Kimberly Ennico Smith, an astrophysicist, will be among the 20-strong crew to actually be on board for some of the 25 missions.
"In your winter the water vapour in the atmosphere drops down pretty low so it's extremely clear here," she said, despite the fact that much of the country has been saturated in rain this week.
"It's fascinating, it is really cool because you're actually looking at things that no-one else can see and we're looking at these wavelengths that our eyes can't see so we are really peering into the universe with new eyes."
Sofia's missions are highly varied and deeply complex.
"As an observatory that allows us to study the universe in the infra-red we can see the fundamental makeup of our universe. In a sense we're viewing our molecular universe, our cosmic origin," Ennico Smith said.
"We're studying the life cycle of stars - from their birth to their death and every time in between and perhaps even their pre-birth, which is a big mystery. We still don't know how stars are formed.
"Particularly at this time of year and from these southern latitudes we can see the centre of the Milky Way. We can also study the Magellanic Clouds which you cannot see from up north."
Last year, Herald reporter Kurt Bayer got the rare chance to join Sofia on of its missions.