Cassini's closest approach, within 474 km of Dione's surface, will occur at 12.03 a.m. (Indian Standard Time).
The scientists expect fresh images to begin arriving on Earth within a couple of days following the encounter.
Dione has been an enigma, giving hints of active geologic processes, including a transient atmosphere and evidence of ice volcanoes.
"But we have never found the smoking gun. The fifth flyby of Dione will be our last chance," said Bonnie Buratti, Cassini science team member at Nasa's Jet Propulsion Laboratory in Pasadena, California.
Gravity-science data from the flyby will improve scientists' knowledge of the moon's internal structure and allow comparisons to Saturn's other moons.
Cassini has performed this sort of gravity science investigation with only a handful of Saturn's 62 known moons.
During the flyby, Cassini's cameras and spectrometers will get a high-resolution peek at Dione's north pole at a resolution of only a few feet.
In addition, Cassini's "Composite Infrared Spectrometer" instrument will map areas on the icy moon that have unusual thermal anomalies those regions are especially good at trapping heat.
Meanwhile, the mission's "Cosmic Dust Analyzer" continues its search for dust particles emitted from Dione.
This flyby will be the fifth targeted encounter with Dione of Cassini's tour at Saturn.
"This will be our last chance to see Dione up close for many years to come," said Scott Edgington, Cassini mission deputy project scientist.
Cassini's closest-ever flyby of Dione was in December 2011 at a distance of 100 kms.
Cassini's sharp views revealed the bright features to be a system of braided canyons with bright walls.
Cassini has been orbiting Saturn since 2004.
After a series of close moon flybys in late 2015, the spacecraft will depart Saturn's equatorial plane to begin a year-long setup of the mission's daring final year.
For its grand finale, Cassini will repeatedly dive through the space between Saturn and its rings.
Catch the latest from the Consumer Electronics Show on Gadgets 360, at our CES 2026 hub.