John and Thady Gosden's globetrotter has won big races in England, Dubai, France and Saudi Arabia throughout his career and will attempt to add America to his decorated CV before he heads to France to stand as a stallion.
It has been a somewhat frustrating season for the son of Make Believe, who was slowly away and encountered trouble in running when second at Sandown in the Eclipse, before set the mammoth task of trying to take down Baaeed in defence of his Juddmonte International crown.
The ground was against the five-year-old in both the Irish Champion Stakes and Prix de l'Arc de Triomphe, but connections believe he has "got his mojo back" since arriving in Kentucky and are optimistic of one last day in the sun in the $4m contest.
"It's a bittersweet thing, it's his last run before he goes off to stud and I'd love for him to get his head in front," said Ted Voute, racing manager to Mishriff's owner Prince Faisal.
"It's been a long season of seconds and thirds, but from what I've seen from being here he has got his mojo back, I think. Everyone says he looks great and to my eye he looks great, so let's see if the final outing comes up with the Barathea result.
"He seems to thrive on these long journeys, he's strutting around the place like he owns it again and maybe that is what has been missing for part of the year. It would be a lovely ending and we deserve to be here, and we deserve to be competitive.
"So far he hasn't put a foot wrong out here and seems to have enjoyed it. Frankie has ridden him the last two days and seems happy with what's underneath him so we can only hope."
Main Sequence (2014) and Highland Reel (2016) are the only two winners of the Turf from a double-figure stall in the past 10 years, but the Mishriff team are hopeful Dettori's experience at the Breeders' Cup can help navigate a winning passage from his wide draw in 11.
"The draw is not ideal, but I think he will still have plenty of time," continued Voute.
"It (the draw) wasn't ideal either in the Sheema Classic and that was a mile and a half, and I think the start was even closer to the bend. Looking at the make-up of the track there is plenty of time for Frankie to do his stuff - he has plenty of experience on these tracks and I'm sure John will leave things up to him.
"Mishriff has been a fantastic horse for Prince Faisal and during lockdown he kept us all inspired and has taken us all round the world. It is bittersweet it is coming to an end - it has been a great to be involved in his journey and it is what keeps us all motivated. I thank Mishriff from the bottom of our hearts and I'm going to miss him."
The British challenge is headed by Charlie Appleby's pair of Nations Pride and Rebel's Romance as the Moulton Paddocks handler looks to not only enhance his own imperious Breeders' Cup record but win the race for a second time following Yibir's win in 2021.
Both know what it takes to succeed overseas with Nations Pride a winner of both the Saratoga Derby and a Grade Three most recently, while his stablemate Rebel's Romance is unbeaten in his last four, scoring in Germany the last twice.
"For me you can't fault what Nations Pride has achieved over here and while he's not the finished model yet, we are where we want to be with him. He's essentially a mile-and-a-quarter horse who will get a mile and a half round here," said Appleby.
"In contrast Rebel's Romance is a solid mile-and-a-half horse who doesn't have the same level of acceleration and it will be more of an effort for him to be going around two turns."
Aidan O'Brien has tasted plenty of success in the race and saddles two as he searches for win number seven. The master of Ballydoyle is putting his trust in last year's runner-up Broome who will once again be partnered by Irad Ortiz Jr, while one-time Derby candidate Stone Age is the mount of Ryan Moore.
The Europeans have won this seven times in the last 10 years and hold an obvious strong hand once again, but the best of the home contingent may well be Bill Mott's War Like Goddess.
The five-year-old was beaten less than a length when third in the Breeders' Cup Filly & Mare Turf at this meeting last year and arrives having won three of her last four outings.
"She's been very competitive with whoever we've thrown her in with, she was probably as good as anybody in the Flower Bowl. She didn't win that day, but she was trapped down inside and just really didn't get the trip, she was the victim of an extremely slow pace that day," said Mott.
"Other than that, she always shows up and comes and runs her race, she displayed her talent the other day against the boys. Of course, there's going to be new shooters and we're going to have some horses from Europe, all the best will be there so it's going to be another fun race.
"She's a really good filly, she's very special and I'm anxious to see how she does against this group. We chose the 12-furlong race against the boys because of the distance, rather than going to the Filly & Mare Turf which is only a mile and three-sixteenths at Keeneland. We just felt that she is probably better at the longer distance and able to compete with better horses at that trip."