Niko Kovac's men made their return to the Champions League with a third-placed finish last term, while Nantes retained their top-flight status by the skin of their teeth.
Inconsistency in the first half of the 2020-21 campaign ultimately proved costly in Monaco's bid for the Ligue 1 title, but Kovac's men kept pace with Lille and Paris Saint-Germain right up until the final knockings of the season before claiming third spot - five points adrift of the champions.
In doing so, Les Monegasques claimed that coveted spot in the Champions League which they so richly deserved, and their continental campaign began earlier this week against Sparta Prague, who were no match for Kovac's well-drilled unit in the first leg of their third qualifying round tie.
Fielding a highly recognisable lineup from their 2020-21 endeavours, Monaco struck through Aurelien Tchouameni and Kevin Volland to take a 2-0 lead back to the French Riviera, and a clash with Genk or Shakhtar Donetsk for the right to play in the group stages surely awaits Les Monegasques.
While Monaco's final pre-season encounter ended in a 2-1 defeat to Real Sociedad, Kovac oversaw victories against Wolfsburg, Red Bull Salzburg and Cercle Brugge during the exhibition period, and Les Monegasques ended the 2020-21 Ligue 1 campaign with seven wins from their final nine encounters - conceding a mere three goals in that run.
The principality side came agonisingly close to a piece of silverware in the form of the Coupe de France only to be outclassed by serial winners PSG in the final, but Monaco are certainly in good hands with Kovac and have every right to be eyeing another title charge in the French top flight.
Forced to do it the hard way in their bid to stay up, Nantes' revival under Antoine Kombouare was not enough to prevent them registering an 18th-placed finish and a spot in the promotion/relegation playoff with Toulouse.
Les Canaris embarked on a four-game winning streak to give themselves a glimmer of hope before the final day of the season, but a 2-1 defeat to Montpellier HSC would condemn them to a bottom-three standing, and they survived courtesy of the away goals rule following a 2-2 draw with Toulouse over two legs.
It proved to be third time lucky for Nantes after Christian Gourcuff and Raymond Domenech were given the boot before Kombouare's appointment, but the former PSG coach has hardly been able to take inspiration from his side's pre-season endeavours.
Indeed, Les Canaris claimed a 1-0 success over Guingamp and an impressive 3-1 win over Brest, but they would proceed to lose Caen, Niort, Lorient and Ligue 1 new boys Clermont - not exactly an inspiring run of form before another inevitable fight to keep pace with the big boys in the top division.
Furthermore, Nantes travel to the Stade Louis II on a six-game losing streak against Monaco, who claimed a pair of 2-1 victories over Les Canaris last season, and Friday's visitors have not won this battle on the road since both sides plied their trade in Ligue 2 during the 2012-13 season.
Monaco defensive mainstays Benjamin Lecomte and Guillermo Maripan were forced to sit out the first-leg win over Sparta Prague due to injury, with the former's absence likely handing Bayern Munich loanee Alexander Nubel his first Ligue 1 start in goal.
Youthful attacker Krepin Diatta (knee) could also be missing from Friday's squad, but Monaco have struck a deal for Dutch starlet Myron Boadu, who follows Jean Lucas and Ismail Jakobs to the club on a permanent deal.
Boadu's signing comes after Stevan Jovetic completed a move to Hertha Berlin, and the club have also waved goodbye to two full-backs in Benjamin Henrichs and Fode Ballo-Toure, who have joined RB Leipzig and AC Milan respectively.
Meanwhile, Nantes already have a suspension concern to work around as Pedro Chirivella is banned for this game due to an accumulation of bookings from last season, which should see loan signing Wylan Cyprien link up with Ludovic Blas or Samuel Moutoussamy in the middle.
Randal Kolo Muani - who represented France at the Tokyo 2020 Olympics - has more or less confirmed that he will remain at the club for the 2021-22 season amid links with AC Milan, and his return from Japan comes at an ideal time with Kalifa Coulibaly (thigh) out for at least three weeks.
Monaco possible starting lineup:
Nubel; Aguilar, Disasi, Badiashile, Henrique; Golovin, Fofana, Tchouameni, Diop; Ben Yedder, Volland
Nantes possible starting lineup:
Lafont; Appiah, Pallois, Castelletto, Fabio; Coco, Cyprien, Moutoussamy, Blas; Simon, Kolo Muani
We say: Monaco 2-0 Nantes
Friday's opener does not exactly have a blockbuster billing, but Monaco will know the importance of a fast start to the season after their early inconsistency proved fatal last term.
Kombouare's Nantes were the team to beat during the back end of the 2020-21 campaign, but they are unlikely to experience much joy against Monaco, who should claim a comfortable success on the opening day.