Roberto Martinez's men have their eyes firmly on the prize as the number one ranked nation in the world, while Russia have realistic expectations of a top-two finish in the group.
Forty-one years on from their unsuccessful venture in the 1980 tournament - which saw Belgium fall victim to the prowess of West Germany in the final - Martinez will endeavour to lead the world's top-ranked nation to the maiden international honour which they so crave.
A flawless qualification period for Euro 2020 saw Belgium qualify with 30 points taken from a possible 30, but the heartache of 2016 still lingers in the memories of the players involved in that infamous summer, when Wales stunned the continent to prevail 3-1 and dump the Red Devils out in the quarter-finals.
That tournament represented Belgium's first appearance at the Euros since 2000, but their meteoric rise over the past decade means that they are among the favourites to go all the way this summer, and failing to top a group comprising Russia, Denmark and Finland would be nothing short of disastrous.
Martinez was not treated to the goal-laden performances he has become accustomed to seeing from his side in their warm-up matches, though, as Greece held Belgium to a 1-1 draw before a 38th-minute Romelu Lukaku strike was all it took to get them over the line against Croatia.
Nevertheless, Belgium enter the Euros on the back of a nine-game unbeaten run across all competitions, and with plenty of talented individuals in their ranks to boot, so the Red Devils need no added incentive to lay down a marker on the first matchday against their ever-hopeful opponents.
Similarly, Russia more or less blew the competition out of the water to secure progression into the finals tournament, with two defeats to upcoming opponents Belgium the only blips for Stanislav Cherchesov's men en route to the Euros.
During the days of the Soviet Union, the inaugural competition in 1960 - then a mere four-team tournament - ended with Russia lifting the trophy aloft, but a semi-final appearance in 2008 for an Andrey Arshavin-inspired Russia has since been their only standout performance amid a spate of group-stage exits.
Three years on from welcoming the world's best to Russia for the 2018 World Cup, Cherchesov's side are far from guaranteed a knockout berth at the Euros with Denmark also occupying a place in Group B, and only a late Aleksandr Sobolev penalty could propel them to victory in a friendly with Bulgaria last weekend.
A somewhat dissatisfactory Nations League campaign preceded two wins from their opening three games of World Cup qualification, and while Russia's recent form is certainly mixed to say the least, only 11 perfect individual performances will do if they are to get one over the number one ranked team in the world.
Belgium secured 3-1 and 4-1 wins over Russia when the sides locked horns during qualifying for Euro 2020, and the Red Devils are unbeaten in their seven meetings with Saturday's opponents, whose most memorable result in this fixture was a 3-3 draw in a 2017 friendly.
Belgium's influential playmaker Kevin De Bruyne has been forced to go under the knife for facial fractures sustained in the Champions League final, and he has not travelled with the squad to St Petersburg.
The Manchester City man is joined on the sidelines by Axel Witsel - missing out on a return to his former home following his stint with Zenit St Petersburg - with an Achilles issue, while the injury-plagued Eden Hazard may not be risked from the off just yet.
Leandro Trossard and Dedryck Boyata have shaken off knocks and should be available to Martinez, but it would be a surprise to see either man start, with Jan Vertonghen and Thorgan Hazard expected to get the nods.
Sticking with the theme of facial injuries, Russia midfielder Dmitri Barinov took a blow to the nose and had to be taken off against Bulgaria, but the 24-year-old ought to be fine for the opening encounter.
Roman Zobnin has also shaken off an unspecified issue, but veteran defender Fedor Kudryashov will play no part against Belgium due to a calf problem, and Roman Evgeniev has been called up to the squad to replace Andrey Mostovoy following a positive coronavirus test.
Sobolev's late winner against Bulgaria is unlikely to see him rewarded with a start over Artem Dzyuba, as the 6ft 6in forward aims to hit 30 goals for the national team and go level with all-time top scorer Aleksandr Kerzhakov.
Belgium possible starting lineup:
Courtois; Alderweireld, Denayer, Vertonghen; Castagne, Tielemans, Dendoncker, Carrasco; Mertens, Hazard; Lukaku
Russia possible starting lineup:
Shunin; Barinov, Dzhikiya, Semenov; Fernandes, Zobnin, Ozdoev, Kuzyaev; Miranchuk, Golovin; Dzyuba
We say: Belgium 2-0 Russia
A Belgium team with the likes of Hazard and De Bruyne firing on all cylinders would have no problem marching to a comfortable success in this fixture, but Russia may sense an opportunity against the injury-hit Red Devils.
Cherchesov's side have flattered to deceive in recent months, though, and after beating them twice in qualification, we can envisage a third consecutive victory for Belgium to kick off their Euro 2020 dream in perfect fashion.