Mikel Arteta's Gunners are a single point above Pep Guardiola's men with three games left but City, who host Wolves, crucially have a game in hand.
Newcastle can pile the pressure on Manchester United in the battle for a Europa League place if they win at Burnley, who are plotting a great escape.
AFP Sport looks at three talking points ahead of the action.
Can Wolves stop City juggernaut?
Arsenal have hit a rich vein of form since their 2-0 defeat by Aston Villa last month, but are competing against a City side who are now unbeaten in 31 games in all competitions.
The Gunners have a chance at least to apply some pressure by beating Bournemouth in the early kick-off at the Emirates on Saturday.
Bournemouth have registered their highest-ever points tally in a Premier League season to climb to 10th spot but have only beaten Arsenal once before.
City were not at their best against Nottingham Forest last weekend but still found a way to win and are strong favourites to wrap up an unprecedented fourth straight English title.
Arsenal will cling to the hope that Wolves can complete a rare double against City after they won 2-1 at home earlier this season.
Guardiola, for his part, does not believe his side can afford to drop any points in the run-in.
"With four games left, it's like climbing a mountain," he said. "They are very tough games... If we draw a game, we are not going to win the Premier League. It is what it is."
Man Utd seek to stop rot
Manchester United's sorry season could plumb new depths unless they kick their costly habit of conceding late goals.
Erik ten Hag's chaotic team have won just two of their past nine Premier League matches and have tricky games to come against in-form Crystal Palace, Arsenal and Newcastle, who are their closest rivals for a Europa League spot, before they face Brighton on the final day.
United have two potential routes into the Europa League, either by beating Manchester City in the FA Cup final or finishing sixth in the Premier League.
Seventh place could also be enough for Europa Conference League football next season.
The Red Devils have never finished below seventh in the Premier League but that is far from certain to remain the case given their poor form.
West Ham and Chelsea are within striking distance but have been hampered by their own inconsistency in recent months.
Burnley's escape attempt
Burnley appeared dead and buried just weeks ago but they have lost just one of their past eight league games to remain in the battle for survival.
Vincent Kompany's team are still second from bottom of the table but are just two points from safety with three matches to play.
The first of those is at Turf Moor against Eddie Howe's Newcastle, who have lost 10 times on the road this season.
Burnley's final game is on May 19th against Forest, currently one place above the drop zone, and Kompany wants his team to be still alive when the teams meet.
"For us, the biggest thing is, can we give ourselves a game against Forest where we have something to look forward to?" said the Belgian.
"We don't need much more. We just want that opportunity on that one day. That's enough for us to rally to something special."
Forest will hope to pull away from the danger zone when they travel to already relegated Sheffield United.
