The Panamanians, meanwhile, are making their maiden appearance at the tournament proper and will be aiming to give a good account of themselves by avoiding a heavy defeat on the global stage.
Belgium manager Roberto Martinez is a man under pressure, despite losing only one match in charge of the national team since his tenure began in 2016.
With a squad comprising some of the world's most talented players, the Spaniard has a huge task on his hands succeeding where his predecessors have failed.
The Red Devils aced their qualifying group, winning all but one of their 10 matches to top the pile with 28 points, nine more than runners-up Greece.
Fast-paced, attacking football has been the driving force behind their success, and the Belgians netted a whopping 43 goals on the road to Russia, more than any other European nation.
Former Everton man Lukaku was in solid form during qualifying, racking up 11 goals in 10 matches, while Chelsea's Eden Hazard was also a key figure, providing six goals and five assists.
Belgium have maintained their unbeaten run in their World Cup warm-up fixtures, winning four out of six friendly matches and conceding just one in their last five games.
They head into the match against Panama off the back of a 4-1 demolition of Costa Rica, who came through the same CONCACAF qualifying group as the Red Devils' Group G opponents.
Recent form: DWWDWW
Panama have been dubbed the weakest team in the tournament on paper and are thus tipped to end up on the wrong side of a heavy defeat against the Belgians.
Their greatest strength is arguably their manager Hernan Gomez, who is the only member of their camp with prior World Cup experience, having coached Colombia and Ecuador at the finals in 1998 and 2002 respectively.
Los Canaleros have already defied the odds by qualifying for Russia, booking their place there at the expense of the United States in dramatic fashion.
The CONCACAF qualifying zone went down to the wire, with Gomez's men producing an 87th-minute winner to defeat Costa Rica, while the US lost to Trinidad and Tobago, to secure their spot in the finals.
The World Cup debutants have played eight friendlies since qualifying and won only two of those.
Goals have been a problem for the Central Americans, as they have netted just one in their last five international outings, which include a 1-0 loss to Norway, a goalless draw with Northern Ireland and a 6-0 clobbering at the hands of Switzerland.
Panama were dealt a major setback while preparing for Russia when their star player, winger Alberto Quintero, was ruled out of the tournament through injury, forcing Gomez to call up KAA Gent's Ricardo Avila in his place.
Without Quintero, any result beyond a heavy defeat would be considered a feat against the Belgians.
Recent form: DLLWDL
Manchester City defender Vincent Kompany is likely to be benched for Belgium's opener due to concerns over his fitness, with Laurent Ciman of Los Angeles FC touted as a possible replacement at centre-back.
Michy Batshuayi is also an injury concern for Martinez and may be left out of the squad entirely.
The Red Devils are expected to line up in a 3-4-2-1 formation, with Lukaku operating as a lone striker with support from Hazard and Napoli's Dries Mertens.
Meanwhile, Panama may be forced to gamble on the fitness of centre-back Roman Torres, due to a lack of viable replacements, while Avila is likely to be handed a key midfield role.
Belgium possible starting lineup: Courtois; Alderweireld, Ciman, Vertonghen; Meunier, Carrasco, Witsel, De Bruyne; Mertens, Eden Hazard; Lukaku
Panama possible starting lineup:
Penedo; R. Torres, Escobar, Machado, Ovalle, Murillo; Gomez, Avila, Barcenas, Godoy; G. Torres
Head To Head
This will be the first time that Belgium and Panama have played against each other.
We say: Belgium 5-0 Panama
Not only would it be a shock if Belgium fail to defeat one of the World Cup's lowest-ranked sides, it would also be a surprise if they failed to do so by a significant margin. The likes of Lukaku, Hazard and Kevin De Bruyne will prove too much for a Panama team that have shipped seven goals and netted only one in their last four matches.