A season of abject failure under David Moyes brought a swift end to the former Everton manager's reign at Old Trafford and United will have to act equally decisively to install the right man to try to revive their fortunes.
Netherlands manager Louis van Gaal is the favourite and he has the necessary experience and record of success.
Carlo Ancelotti of Real Madrid and Borussia Dortmund's Juergen Klopp have also been linked with the job, although the German appeared to rule himself out of contention on Tuesday.
But bringing in at least four top-quality internationals and moving out several ageing players and serial under-performers will not be an easy task.
The United defence needs a complete overhaul.
Centre backs Rio Ferdinand and Nemanja Vidic were key players in United's success under Alex Ferguson but Vidic is joining Inter Milan and Ferdinand, 35, is also long past his sell-by date.
French left back Patrice Evra has given sterling service in eight years at the club but he too should be allowed to leave along with firebrand Brazilian right back Rafael, a talented attacking player but defensive liability.
Then there is the midfield, for so long a major strength of United sides under Ferguson with the likes of Roy Keane, Paul Scholes, David Beckham and Ryan Giggs contributing so much in their contrasting styles.
Moyes had to rely on the experienced but one-paced Michael Carrick as his central linchpin and the acquisition of the skilful and creative Juan Mata failed to address United's glaring issue in the centre of the pitch - a lack of speed.
Darren Fletcher is a disciplined player and a solid shielder of the defence but his lack of creativity will always be exposed at the highest level while Tom Cleverley has failed to show the necessary quality.
The signing of Marouane Fellaini from Moyes's former club Everton, a panic buy for 27 million pounds ($45.4 million) at the end of the pre-season transfer window, will go down in history as a microcosm of the manager's doomed stay at the club.
The lanky long-haired midfielder has looked like a fish out of water at United, failing to score a goal and frequently lumbering ineffectively around the centre of the pitch.
He must also be moved on along with Japanese playmaker Shinji Kagawa who has had limited opportunities to prove his worth but looks too similar to Mata to be accommodated in the same team.
Moyes rarely played with two wingers, a cornerstone of Ferguson's success, but the emergence of 19-year-old Adnan Januzaj was a beacon of hope in a depressing season.
The highly inconsistent Ashley Young and Nani must also be moved on, though pacy and disciplined right winger Antonio Valencia may have a future at Old Trafford.
Perhaps Moyes's best achievement at United was persuading England striker Wayne Rooney to stay and his form has been consistently good in a difficult season.
The same cannot be said of Robin van Persie, whose 26 league goals fired United to the title 12 months ago in Ferguson's last season in charge.
The Dutch striker has been a peripheral figure under Moyes, plagued by the injuries which afflicted him at former club Arsenal and clearly unhappy at playing in a losing team.
England forward Danny Welbeck has shown flashes of his ability but the Manchester-born 23-year-old hinted last week that he was unhappy at Old Trafford and he could also leave.
One plus has been the reliability of young Spanish goalkeeper David De Gea and he will stay at United, a player along with Rooney, Januzaj, Mata and young defenders Phil Jones and Jonny Evans for the new manager to build a team around.
United have been linked with some of the best players in the world.
Bayern Munich's German midfielder Toni Kroos, Paris St Germain striker Edinson Cavani and young Southampton left back Luke Shaw are reportedly on the club's radar.
All fit the bill in terms of the quality United need but the new manager will face fierce competition to secure their signatures and will not be able to offer them European football next season.
There are tough times ahead for Manchester United. They must choose the right manager to negotiate them.