Eastern Conference heavyweights New York City and the Philadelphia Union clash at Citi Field on Saturday with the home side desperate to kick-start a play-off push.
New York, the 2021 MLS champions, were beaten by Philadelphia in last year's Eastern Conference final but have struggled this season and are 10th in the East with just four wins from their opening 13 games.
Coach Nick Cushing, the former Manchester City women's team manager, has had to partially rebuild the team after the exits of their main attacking threat Maxi Moralez, goalkeeper Sean Johnson and Peruvian defender Alex Callens.
The team has yet to gel and go into the match after a four-game run on the road in which they collected just a solitary point.
Cushing told the players at the training ground, in a video released by the club, that the four matches had revealed a lot about the state of his squad.
"We've learnt a lot about ourselves, individually and as a team. Who we want to be is up to us," Cushing said.
"If we want to be a proper team we can be. We can be a real special team but we can also be a real average team," he added, urging the players to 'invest' more in their efforts.
Last season, Philadelphia won both regular season clashes with NYCFC and they certainly enjoy the upper hand in current form.
Jim Curtin's team are unbeaten in six games, winning four of them and after a slow start to the season, influenced by their involvement in the CONCACAF Champions League, the Union have moved up to fifth.
New York will have to keep a close eye on the Union's Hungarian attacking midfielder Daniel Gazdag, who has six goals in 12 games.
While Philly have progressed in recent weeks, it is Cincinnati who are the pace-setters in the East, five points clear of Nashville.
Cincinnati head to Colorado to face the Rapids having won three straight games and with just one defeat so far this season.
Nashville, unbeaten in six, are in action on Sunday at home to the Columbus Crew.
Western Conference leaders and defending champions Los Angeles FC have a bye week ahead of their CONCACAF Champions League final, first leg, away to Mexico's Leon on Wednesday.
That offers the Seattle Sounders a chance to take over at the top of the West if they can take care of business at home to the New York Red Bulls.
The Red Bulls have enjoyed a bounce in form since Gerhard Struber was replaced as coach by Troy Lesesne with the New Jersey side enjoying two wins at home and a draw at Toronto.
FC Dallas, fourth in the West, travel to fifth-placed San Jose.