Rarely has an edition of the three-week Spanish duel featured such a high-calibre line-up with the reigning champions of all three Grand Tours on the start line.
Dutch outfit Jumbo Visma look formidable after naming Tour de France winner Jonas Vingegaard (26) and Giro d'Italia overall champion Primoz Roglic (33) as joint leaders.
Defending champion Remco Evenepoel (23) (Soudal–Quick-Step) will have something to prove after a COVID-19 positive test eliminated him from this year's Giro while he was wearing the maglia rosa, while Ineos Grenadiers have the experienced Geraint Thomas (37) and Egan Bernal (26) as their GC options.
Mallorcan Enric Mas (28) (Movistar) is one of several Spanish riders looking to make an impact, especially after he was forced to abandon the Tour de France after a crash on stage one.
Spain's Juan Ayuso (20) (UAE Team Emirates) will also be one to watch but the focus for the battle for the maillot rojo will be very much on three-time Vuelta champion Roglic and Vingegaard and just how Jumbo Visma play their cards over the 21 stages and 3,100km to Madrid - a route that includes nine summit finishes.
Should either win overall it would be the first time a single team has won all three Grand Tours in a season.
"I think the battle will be to find Jumbo's weak point," Spanish great Alberto Contador, who will be analysing the race for Eurosport GCN, said ahead of the start.
Sprinters will have a few opportunities to make their mark but as has become tradition, La Vuelta a Espana is stacked with brutal days of horribly steep tarmac suited to the best climbers in the business. And the race is brimming with them.
Slovenia's Roglic is bang in form after winning this month's Vuelta a Burgos and is looking to be the first rider to claim the Giro-Vuelta double since Contador in 2008.
The biggest threat to that ambition will come from within his own camp with Denmark's Vingegaard having shown at the Tour de France that he is seemingly unbreakable in the mountains.
Were Vingegaard working in support of Roglic or vice versa, a Jumbo Visma victory would surely seem assured barring accidents, but the fact they will be battling each other will inject some unpredictability and an intriguing sub-plot to the race.
Vingegaard has not raced since clinching his second Tour de France title in Paris so there might be some early doubts that Roglic could try to exploit during a mountainous stage three in Andorra.
"On paper, Roglic has the better chance," Philippe Gilbert, also part of Eurosport GCN's coverage team, said.
"He has the best preparation and has shown good form at Burgos and was really strong there. Vingegaard went deep at the Tour and it was a hard Tour. I spoke with a lot of riders and they were so deep in their reserves mentally and physically."
While Belgian dynamo Evenepoel, rated as the most exciting rider in men's racing by Contador, will have his work cut out to repeat his 2022 triumph, writing him off is foolhardy.
He might not have a team of Jumbo Visma's depth to offer assistance in the mountains but if anyone can take a race by the scruff of the neck it is the 23-year-old.
The action begins on Saturday with a 14.8km team time trial around Barcelona while the hilly 182 km stage two starts in Mataro and finishes at Barcelona's Montjuic.
