After a tumultuous first half of the season at White Hart Lane, Spurs start 2014 with the unenviable task of facing David Moyes' title holders at Old Trafford.
United themselves endured a tough start to the campaign as they began life without Sir Alex Ferguson, but there are now signs of a revival.
They head into the match on a run of six successive wins in all competitions and sixth in the Barclays Premier League, eight points off the top.
United will undoubtedly be Sherwood's toughest test since he replaced Andre Villas-Boas and one the Spurs boss suggested will mean he has to alter his attack-minded philosophy.
"I like to play with risk," the Tottenham manager said after overcoming Stoke 3-0.
"There is going to be, with respect to Stoke, tougher tests ahead and we know that.
"We have to try to find the right formula to perform against some of the bigger teams.
"We have to assess what Man United are coming with. We know they're going to be very, very good.
"They always are and have been ever since I was in football. We know we have to give them respect but we can't be lambs to the slaughter.
"We need to make sure we go out there and impose ourselves on them as much as we can."
West Brom, Everton and Newcastle have all shown it is possible to do that this season, with all three winning league matches at Old Trafford.
In fact, United have only won four of their nine home matches and Spurs head to the north west buoyed by last term's 3-2 victory.
"They're turning it around and they are on a run," Sherwood said. "We know from history when they are on a run, they get a head of steam and are very hard to stop.
"We've got to try and find a way of stopping them in their tracks to get something positive for ourselves.
"We won last year there. Gareth Bale scored a great goal, so they've already been there and imposed themselves on Man United. Hopefully they can use that as an experience to go forward.
"It is a big arena, a fantastic football stadium but it will only be nice if we get a result."
Tottenham's chances of continuing their unbeaten start to league life under Sherwood will be made all the more tougher at Old Trafford by their mounting injury problems.
While they can welcome back Kyle Walker from suspension, Sandro, Younes Kaboul, Andros Townsend and Jan Vertonghen remain sidelined through injury.
Jermain Defoe and Danny Rose are doubts, while it has been confirmed Paulinho will miss the next four weeks through an ankle ligament injury.
The Brazil midfielder, who had been impressing in his first start under Tim Sherwood, was forced off 62 minutes into Sunday's 3-0 win against Stoke after being clattered by Charlie Adam.
The Stoke midfielder avoided a booking for the challenge but not the anger of Tottenham fans and staff, as this was the fourth time he has been involved in a high-profile incident against Spurs.
During his time with Blackpool, Liverpool and Stoke, the 28-year-old has previously clashed with Bale on two occasions and once with Scott Parker.
Tottenham's anger at yet another incident was clear in a statement on Paulinho's condition released on Tuesday morning, unusually highlighting the perpetrator's role in the incident.
"Following a MRI scan, the club can confirm that Paulinho has sustained significant ligament damage to his right ankle after a heavy challenge from Charlie Adam during Sunday's win against Stoke City," read a statement on the club's official website, www.tottenhamhotspur.com.
"The Brazil international was forced off as a result of the injury and is expected to be sidelined for at least four weeks."
Tottenham are reportedly considering making a formal complaint about Adam, who came close to moving to White Hart Lane from Blackpool in January 2011.
The Stoke midfielder's challenge on Paulinho also led Spurs and Brazil team-mate Sandro to wade into the debate, if only in tongue-and-cheek style.
The 24-year-old posted "Charlie Adams - THE BEAST IS WATCHING YOU!!!" via his Twitter account, with a link to a photo of him staring ominously into a camera.