Manchester United boss David Moyes will take in his first reunion with Everton on Wednesday, while Fulham's rebuilding project starts after the sacking of Martin Jol with a derby date against Tottenham Hotspur.
League leaders Arsenal will be hoping to avoid becoming another prized scalp for Hull City, Liverpool will be looking to bounce back from their KC Stadium reversal against Norwich City, Chelsea travel to Wearside to face Sunderland and Manchester City will be seeking a cure to their travel sickness away at West Bromwich Albion.
Elsewhere, Southampton need to get back on track against Aston Villa, Stoke City and Cardiff City have plenty to play for at the wrong end of the table and Newcastle will want to maintain their momentum when they go to Swansea City.
On a busy night of Premier League action, the most intriguing tussle will take place at Old Trafford, as Moyes welcomes his former club to the home of his current employers. The Scot spent 11 years in charge of Everton before accepting the unenviable task of succeeding Sir Alex Ferguson at Manchester United. Critics were quick to question early on whether the Red Devils had made the right choice, but a run of 12 games without defeat in all competitions has helped to silence the detractors. United are, however, still nine points off the pace in the title race and will need no reminding that Everton have suffered just one setback this season. That reversal did come in Manchester, though, with City proving too strong for the Toffees back in October.
The side United and a clutch of other clubs are trying to chase down are Arsenal, with the Gunners having opened up a four-point lead at the summit. They have dropped just eight points so far this season and boast the joint-best defensive record in the division. Arsene Wenger's side have cleared many of the hurdles placed in front of them so far and will be looking to negotiate another when buoyant Hull City roll into north London. The Tigers have been something of a surprise package this term, but showed on Sunday that they cannot be underestimated as they put a serious dent in the title aspirations of high-flying Liverpool. Hull know what it takes to win at the Emirates - having prevailed 2-1 back in 2008 - and have shown already this season that they have little regard for reputation.
Putting a shock reversal in East Yorkshire to the back of their mind will be the priority for Liverpool when they welcome Norwich City to Anfield. The Reds have responded to their previous two Premier League defeats this season with resounding successes in their next top-flight outing, and Brendan Rodgers will be demanding more of the same in midweek. A run of one win in four has seen the Merseyside outfit slip seven points adrift of the frontrunners and they will be aware of the need to remain within touching distance if a sustained challenge for the crown is to be mounted. The loss of Daniel Sturridge to injury represents a serious blow to their title credentials, and Norwich will be hoping that plays into their hands. Chris Hughton's men have picked up useful results against fellow strugglers over recent weeks, but will want to prove that they can also mix it with the big boys.
Another side with something of a point to prove are Tottenham Hotspur - despite their much-improved display against Manchester United on Sunday. A 2-2 draw with the reigning champions has helped to ease some of the pressure on Andre Villas-Boas' shoulders, but Spurs remain without a win in four and down in ninth spot. They will point to the fact that they are only one positive result away from re-joining the top four, but there are issues still in need of address at White Hart Lane. A trip to out-of-sorts Fulham would appear to have arrived at the perfect time, with the Cottagers coming to terms with the dismissal of Jol and the promotion of Rene Meulensteen - a man drafted in as head coach just three weeks ago - as his successor. Fulham desperately need a change in approach to spark them into life, with Jol having paid the price for a run of five straight defeats.
One of only two teams to be sat below the Cottagers at present are Sunderland - a side who have improved under the guidance of Gus Poyet, but one that are still searching for consistency. They may feel that a visit from Chelsea on Wednesday is no bad thing, having often saved their best for the big occasion. Newcastle and Manchester City have already been sent away from the Stadium of Light with their tail wedged firmly between their legs, and the Black Cats will be looking to send Jose Mourinho and his title-chasing troops the same way. Success for Sunderland would not be enough to lift them out of the bottom three, but it would offer another welcome shot in the arm. Chelsea will be in no mood to offer out pre-Christmas gifts, though, as they have clambered into second place. They did come unstuck on their last visit to the north east, against Newcastle, but have been very much back on the points and goal trail of late.
Any slip-up from Chelsea would open the door for Manchester City to continue their ascent up the Premier League standings, but the Blues will first have to find a formula which works away from home. Manuel Pellegrini's side remain perfect at the Etihad Stadium this season, but have collected just four points on their travels. West Bromwich Albion will fancy their chances of piling on the away day misery in midweek, as their home form makes for impressive reading. The Baggies may not have secured as many victories as they would have liked over recent weeks, leaving them glancing over their shoulder, but they are a tough nut to crack and have gone four without defeat at The Hawthorns.
The form team in the division right now are Newcastle United, with Alan Pardew's men having taken maximum points from their four games in November. Stretching that run into December and through the hectic festive period is the challenge now facing the Magpies, with the top four firmly in their sights. Confidence should be soaring when they head to Swansea City, but Michael Laudrup's side did the double over Newcastle last season and need to start replicating those heroics if they are to avoid being dragged into a basement battle. Injuries to key men are not helping the Swans' cause, but they know they have been punching below their weight so far.
The same cannot be said for Southampton who, despite a bit of a wobble, continue to occupy a lofty perch. The Saints have suffered back-to-back defeats to burst their bubble, but remain above the likes of Manchester United and Tottenham in the top-flight standings. A slump through to Christmas must be avoided if they are to remain among those pushing for Europe, and a home date with Aston Villa would be a good place to turn the tide. Villa, though, are unbeaten in four, conceding just twice during that run, and will feel that there is still plenty more to come from them if they can get their most potent attacking weapons firing on all cylinders.
The final fixture of the night sees two sides locked together on 13 points, perched precariously just above the drop zone, go head-to-head at the Britannia Stadium. Stoke City will play host to Cardiff City with both teams aware of the need to start taking points off those in and around them if they are to steer a course to safety. Stoke's Premier League experience could play into their hands during that particular battle, while Cardiff are still getting to grips with life among the elite. Both have shown what they are capable of in glimpses this season, but goals have been in short supply and Mark Hughes and Malky Mackay have been around long enough to know that you will not get very far at the top level without a cutting edge.