The Clarets last faced a top flight team on May 22 when they were consigned to relegation to the Championship following a 2-1 defeat at the hands of Newcastle United at Turf Moor.
This will be the first time that they’ve taken on the Red Devils since February when Paul Pogba and Jay Rodriguez were on the scoresheet, but it will be the club’s first trip to the Theatre of Dreams in 12 months.
The hosts claimed the three points on that occasion as Aaron Lennon grabbed a consolation after Sean Dyche’s side trailed to goals from Scott McTominay, Ben Mee (own goal) and Cristiano Ronaldo.
The latest meeting will have a completely different complexion, however, as Manchester City legend Vincent Kompany has rebuilt Burnley and guided them to the top of the second tier in the process.
United, meanwhile, are now coached by former Ajax boss Erik ten Hag, who has suffered just one defeat in 12 games in all competitions, which was inflicted at Villa Park last month.
Speaking ahead of the fourth round tie, Kompany had said: "It's still a North West derby and I think for us it gives us a chance to measure ourselves against some of the best and see how far we've come and how close we are. That in itself is more exciting for me than the fact that we're going to Old Trafford.”
Here’s how the visitors could line up as they bid for a place in the quarter final of the competition.
. LONDON, ENGLAND - DECEMBER 11: Vincent Kompany of Burnley looks on during the Sky Bet Championship between Queens Park Rangers and Burnley at Loftus Road on December 11, 2022 in London, England. (Photo by Clive Rose/Getty Images)
LONDON, ENGLAND - DECEMBER 11: Vincent Kompany of Burnley looks on during the Sky Bet Championship between Queens Park Rangers and Burnley at Loftus Road on December 11, 2022 in London, England. (Photo by Clive Rose/Getty Images) Photo: Clive Rose
. GK: Bailey Peacock-Farrell
Burnley's Bailey Peacock-Farrell The EFL Sky Bet Championship - Burnley v Millwall - Tuesday 30th August 2022 - Turf Moor - Burnley Photo: CameraSport - Dave Howarth
1. LONDON, ENGLAND - DECEMBER 11: Vincent Kompany of Burnley looks on during the Sky Bet Championship between Queens Park Rangers and Burnley at Loftus Road on December 11, 2022 in London, England. (Photo by Clive Rose/Getty Images)
LONDON, ENGLAND - DECEMBER 11: Vincent Kompany of Burnley looks on during the Sky Bet Championship between Queens Park Rangers and Burnley at Loftus Road on December 11, 2022 in London, England. (Photo by Clive Rose/Getty Images) Photo: Clive Rose
2. GK: Bailey Peacock-Farrell
Burnley's Bailey Peacock-Farrell The EFL Sky Bet Championship - Burnley v Millwall - Tuesday 30th August 2022 - Turf Moor - Burnley Photo: CameraSport - Dave Howarth
3. RB: Matthew Lowton
Burnley's Matthew Lowton takes on Crawley Town's Ashley Nadesan, Teddy Jenks and Tom Nichols The Carabao Cup Third Round - Burnley v Crawley Town - Tuesday 8th November 2022 - Turf Moor - Burnley Photo: CameraSport - Alex Dodd
4. CB: Jordan Beyer
Burnley's Jordan Beyer during the pre-match warm-up The EFL Sky Bet League One - Queens Park Rangers v Burnley - Sunday 11th December 2022 - Loftus Road - London Photo: CameraSport - Rob Newell