Tournament favourites Brazil make their long-awaited World Cup entrance on Thursday when they take on Serbia in Group G.
Switzerland and Cameroon make up a tough-looking pool when they meet in the day's opener.
If that wasn't enough to whet the appetite, there is also the small matter of Cristiano Ronaldo making his first appearance since exiting Manchester United on Tuesday. Ronaldo will captain Portugal against Ghana in Group H.
Another talismanic striker Son Heung-min is expected to be declared fit to lead South Korea against Uruguay, albeit with the use of a facemask.
Here, with the help of Opta data, Stats Perform makes some key predictions ahead of another busy day of action.
All times local.
Switzerland v Cameroon – Al Janoub Stadium (1300)
Cameroon are outsiders in Group G and will be desperate for a good start ahead of some tricky games.
However, the omens for the Indomitable Lions do not look promising. They have conceded four goals in each of their last two games at the World Cup, 4-0 to Croatia and 4-1 to Brazil, and lost their last seven World Cup matches in a row.
Switzerland are renowned as fast starters at the World Cup and are unbeaten in their opening game in their last five appearances.
Player Prediction - Xherdan Shaqiri to score or assist: The Chicago Fire playmaker is Switzerland's all-time top scorer at major tournaments with eight goals in 18 appearances. The former Bayern Munich and Liverpool man loves the big stage and he is likely to be Switzerland's creative hub.
Best Bet - Switzerland to win or draw: Cameroon will be desperate to get off to a winning start - to break their World Cup losing streak - and provide any hope of getting through the group. That is likely to lead to an all-out attacking approach which will leave space for Shaqiri and Breel Embolo to exploit.
Uruguay v South Korea - Education City Stadium (1600)
South Korea's hopes rest largely on the availability of star man Son. But, even if he does play, the Tottenham striker is bound to have concerns going into challenges with the likes of Jose Gimenez and Diego Godin.
Should Son score, he will become just the second South Korean to net in three different World Cups, after Park Ji-sung.
If there is reason for hope for Paulo Bento's men, it is that Uruguay have won their opening match at a World Cup just once in their last seven attempts, in 2018 in Russia against Egypt.
Player Prediction - Luis Suarez to score: Suarez needs one more goal to equal Oscar Miguez (eight) as Uruguay's leading scorer at the World Cup.
Best Bet - Uruguay to win to nil: Uruguay have won all four of their World Cup matches against Asian nations, keeping a clean sheet in three of them. Son, Korea's main attacking threat, is some way short of 100 per cent fitness and it's tough to see how they can threaten Uruguay's physical backline.
— Portugal (@selecaoportugal) November 22, 2022
Portugal v Ghana - Stadium 974 (1900)
All eyes will be on Ronaldo who is now in the unexpected position of having to showcase his ability at the top level as he bids to find a new club following his United exit.
He has form against Ghana, scoring the winning goal as Portugal won 2-1 at the 2014 World Cup.
This could be a high-scoring affair with Ghana averaging the most shots-per-game in the World Cup - since the start of detailed Opta World Cup data collection - among all teams competing in Qatar (19).
Player Prediction - Cristiano Ronaldo to score: Who else? Coming into the 2022 tournament, Ronaldo has scored each of his seven World Cup goals in the group stage; indeed, the Portuguese has scored the most goals in the competition (seven) of any player yet to find the net in the knockout stage (six knockout stage appearances without a goal).
Best Bet - Portugal to score first and win: Portugal have never lost a World Cup game when they've scored the game's first goal (P16 W13 D3), the best unbeaten record in the competition's history.
Brazil v Serbia - Lusail Stadium (2200)
Neymar and Co have an impressive record in the group stage of World Cups - unbeaten in their last 15 games, winning 12 and drawing three. Their last defeat pre-knockout phase came to Norway in 1998 and it's tough to see Serbia changing that statistic.
Neymar has scored 75 times for his country and needs three more to overtake Pele as Brazil's all-time leading goalscorer.
Aleksandar Mitrovic is Serbia's main threat - the Fulham man netted eight times in eight games in qualifying, a record bettered only by the Netherlands' Memphis Depay and England's Harry Kane with 12 - but is facing a race against time to be fit due to an ankle injury.
Match Prediction - Brazil to win and both teams to score: Even if Mitrovic is not fit, Serbia possess plenty of attacking talent with Sergej Milinkovic-Savic, Dusan Vlahovic, Filip Kostic and Dusan Tadic. Brazil have scored four plus goals in 21 games at the World Cup, more than any other team in the tournament's history.
Best Bet - 12 plus corners: Brazil's games saw an average of 12 corners at the 2018 World Cup (60 in 5 games), with only Iceland's games averaging more at the tournament (12.7).