Neil Warnock's men will be hoping to bounce back from consecutive defeats against a side who are winless in their last nine league outings.
The Boro currently sit in 11th position in the Championship table after only picking up three points from their last four matches.
Many tipped promotion specialist Warnock to weave his magic once again in the North-East, but Middlesbrough's recent form has seen them slip six points behind the playoff places.
Goals have been hard to come by so far for Middlesbrough, with just 16 strikes making them the lowest scorers in the top half of the table, but they have been fairly solid at the back. Just 14 goals conceded means they have a tighter defence than table-toppers Norwich City.
The 2006 UEFA Cup finalists have not been in the top-flight since 2017 and were amongst the favourites to return to the Premier League in 2020-21.
A 3-0 loss to Preston North End last time out damaged those prospects, and Warnock's charges will be keen to get their season back on track at the weekend.
Millwall are winless in their last five outings against their upcoming opponents, a statistic that Gary Rowett will not want to hear as he aims to stop the rot in East London.
They currently lie in the bottom half of the table after Tuesday night's draw with Queens Park Rangers made it nine games without a win, a run that has seen The Lions score just four goals.
Rowett's men have not won since October, and their poor form has seen them fall to 17th position, although they are still nine points clear of the relegation places.
Going to a side who are also struggling to pick up three points and put the ball in the back of the net could be the perfect opportunity for the capital club to revive their faltering campaign.
Middlesbrough Championship form: LWLWLL
Millwall Championship form: DDDLLD
That means Duncan Watmore could be in line to keep his starting role with his brace against Swansea at the start of the month the last time Boro bagged a goal.
Rowett will be without midfield man Billy Mitchell, who has yet to recover from a hamstring injury, as well Connor Mahoney, who faces several weeks on the treatment table after picking up a problem with his quad.
Some good news for The Lions' supporters is that striker Kenneth Zohore could be set to make his return from a lengthy lay-off, potentially adding the bite to their attack that has been desperately missing in his absence.
Middlesbrough possible starting lineup:
Bettinelli; Spence, Fry, McNair, Bola; Howson, Saville, Morsy, Johnson, Watmore; Assombalonga
Millwall possible starting lineup:
Bialkowski; Romeo, Hutchinson, Pearce, Cooper; Malone, Leonard, Woods, Wallace, Bennett, Parrott
We say: Middlesbrough 1-0 Millwall
This may not be a clash for the purists, with both sides preferring a more direct approach, but it should be an evenly contested affair.
Middlesbrough have their sights set on the playoff places, and nothing other than the three points will do if they are to avoid losing further ground on the leading pack. Their superior quality should show on the day and secure them a narrow victory.