Manchester City will bid to hammer home their advantage at the top of the Premier League against Southampton, while Manchester United head to Watford hoping to cling onto the leaders' coat-tails in a crucial midweek programme.
City underlined their determination to win the title with a gutsy 2-1 victory at Huddersfield on Sunday as Pep Guardiola's side re-established an eight-point lead over second placed United.
Their Manchester rivals had closed the gap to five points with a 1-0 win against Brighton on Saturday and, with City trailing to a Nicolas Otamendi own goal at half-time against Huddersfield, Jose Mourinho's men were dreaming of a title lifeline.
But City crushed those hopes in gritty fashion as Sergio Aguero's penalty two minutes after the interval eased any nerves from the leaders, who piled on the pressure and were rewarded with six minutes left when Raheem Sterling netted the winner.
City have now won their last 11 Premier League matches and 18 in all competitions.
United can again move to within five points of their hated neighbours if they win at Watford on Tuesday, before City return to action at home to Southampton 24 hours later.
Guardiola admits City's scintillating run will end eventually, but he believes the way his team saw off fired-up Huddersfield should serve as a warning to their rivals that they are fully focused on the title.
"If you want to win the title you can not expect easy games, so we have to live these kinds of situations and we spoke about at half-time how we are going to react in that situation," he said.
"We are going to lose. That is going to happen - definitely. Today was so close - it's going to happen.
"When you play every few days, when you see the scheduling - December, January - we go to Donetsk to play in the Champions League. It's impossible.
"The 18 games in a row is amazing and we have 11 in the Premier League in a row so that's good. We have a good moment and with the spirit we can go further.
"I am pleased because I know our fans are so happy because they see their players fighting until the end."
SHOW OF STRENGTH
United have no margin for error at Vicarage Road, where Watford will aim for a repeat of last season's shock 3-1 win over Mourinho's team.
While Watford impressed in a 3-0 win at Newcastle on Saturday, United laboured to see off Brighton at Old Trafford until Lewis Dunk's own goal from an Ashley Young effort sealed their second successive league win.
United defender Victor Lindelof hopes his side can continue to grind out the wins while they search for their peak form.
"We tried to do our best out there, we tried to play our game but it didn't work out so good," he said.
"We got the three points and that is the most important thing. We didn't play our best game but we got the win and that shows strength."
Champions Chelsea are lagging 11 points behind City in third place and must beat lowly Swansea at Stamford Bridge on Wednesday to have any chance of catching the leaders.
Key to their title defence is Eden Hazard's ability to maintain the fine form he showed in Saturday's 1-1 draw at Liverpool.
Afer an injury-hit start to the season, the Belgian excelled against Liverpool in the number 10 role behind Alvaro Morata.
"The start of this season was full of trouble with Eden because he had an injury with the national team and we started the season without him," Chelsea manager Antonio Conte said.
"Now I think Eden is in really good form and I think he likes to play as a striker. There is a good link with Alvaro."
FIXTURES (10.45pm unless stated)
Brighton v Crystal Palace, Leicester v Tottenham, Watford v Manchester United (11pm), West Brom v Newcastle (11pm)
Arsenal v Huddersfield, Bournemouth v Burnley, Chelsea v Swansea, Everton v West Ham (11pm), Manchester City v Southampton (2000 GMT), Stoke v Liverpool (11pm)