Manchester City, Liverpool, Manchester United, Chelsea and Tottenham Hotspur all face plenty of early tests in the summer and autumn months, and there is the small matter of a World Cup to navigate over the festive period.
Bournemouth, Fulham and Nottingham Forest will all be determined to avoid swift demotions back down to the second tier, and there are several stories to be told elsewhere in the table.
Here, Sports Mole takes on the unenviable task of picking out five Premier League fixtures to look forward to in the 2022-23 season.
Crystal Palace vs. Arsenal - August 5
Where better to start than with the opening day? Two former gritty Premier League midfielders now facing off on the touchline, but there was one clear winner when Patrick Vieira and Mikel Arteta butted heads in the Selhurst Park dugout back in April.
Arsenal's dampening 3-0 loss to their capital counterparts kickstarted a downward spiral that ultimately dashed their top-four hopes, and the Gunners should certainly be out for revenge on that Friday evening.
However, Arsenal kicked off the 2021-22 Premier League season away from home to a London rival in Brentford, and Gooners will not need reminding how that game panned out.
Coincidentally, this game will also mark the third season in a row that Arsenal have begun the Premier League campaign on the road for a London derby having put three past Fulham in 2020-21.
Manchester City vs. Chelsea - May 20
By the penultimate gameweek of the season, we will have a very clear idea as to which teams are still fighting for the highest honours, but there could still be a late twist or two in the tale.
May 20 will see current champions Manchester City prepare for their final Big Six clash of the campaign against Chelsea at the Etihad, and both sides may still be in with a shot of Premier League glory by that point.
The two European powerhouses could also enter the contest off the back of Champions League semi-finals should they progress that far, and Kevin De Bruyne will aim to be the thorn in his former club's side once again after his winner in this fixture back in January.
Arsenal vs. Tottenham - October 1
North London derby fans were blessed with an early meeting between Tottenham Hotspur and Arsenal at the Emirates in the 2021-22 season, and a similar story awaits the two bitter rivals on October 1 this season.
While this North London derby will not make or break either team's season, supporters will welcome the prospect of the two new-look sides jousting for bragging rights on the Emirates turf to hopefully kickstart a positive run of form in an unforgiving autumn schedule.
Tottenham's Champions League and Arsenal's Europa League group-stage campaigns will begin to hot up following the derby, and victory for either side could do them the world of good for their continental endeavours.
Arteta's side won convincingly at the Emirates last season, but Antonio Conte's men responded in kind at their headquarters before pipping Arsenal to fourth place, and it is fair to say that Tottenham are far more ahead in their early transfer business than Arsenal are.
Manchester United vs. Manchester City - January 14
Erik ten Hag's first Manchester derby at Old Trafford should be an electric affair, as by this point, the Dutchman would have had the time to mould the squad into his own vision and integrate any summer signings perfectly.
The seismic shift in power between Man United and Man City over the past 10 years has not always been demonstrated in their derbies, but Pep Guardiola's side will have fond memories of running out 6-1 aggregate winners from their two meetings last term.
Ten Hag has plenty to address before Man City eventually make the journey to the Theatre of Dreams, and the first Manchester derby of the season also lies the same weekend as the first North London derby on October 1.
By January, though, it should become evident what Man United's aims for their first season under Ten Hag are, and this derby also lies in the period with no European football following the conclusion of the World Cup.
Manchester City vs. Liverpool - April 1
Arguably the most highly-anticipated event in the Premier League calendar could once again have major ramifications on the table, as April 1 serves up a treat.
Title favourites Manchester City and Liverpool gear up for what promises to be another enthralling joust on April Fool's Day, but there will be no joking around from Pep Guardiola or Jurgen Klopp at the home of the champions.
Should the Premier League title chase ultimately become another two-horse race between City and Liverpool, the Etihad showdown may give the clearest indication yet as to which way the crown may be heading several weeks later.
Both sides will face further challenging fixtures before the month is up, as well as the prospect of a Champions League quarter-final and FA Cup semi-final, but the business end of the Premier League season could hardly be kicking off in a better way.