The five-time Ballon d'Or winner has enjoyed a stellar season, with 43 goals in all competitions from just 40 games.
The Argentine forward will undoubtedly be eyeing a treble-winning season as he prepares to face United for the first time since scoring against them in the 2011 Champions League final at Wembley.
Smalling is, however, undaunted by the prospect of facing the 31-year-old and, having already come up against Kylian Mbappe and Cristiano Ronaldo this season, he's relishing another tough test at Old Trafford.
"It's something to relish I think," he said.
"This season, we have been lucky enough to face [Cristiano] Ronaldo, [Kylian] Mbappe and they are all challenges that I definitely relish and I think players at this club relish.
"I say bring it on."
And United manager Ole Gunnar Solskjaer - while heaping praise on Messi - echoed the defender's sentiments, whilst pointing out that the Catalan giants possess plenty of other talented players who could cause them problems.
The Norwegian added: "What kind of plan can you have to stop one of the best players in the world?
"[Messi] is a fantastic player. And he will go down in history as one of the best individual players ever. I have to say - he will be difficult to stop but it's never impossible.
"It's not like it is Messi against Manchester United. [Luis] Suarez, [Philippe] Coutinho, [Ivan] Rakitic, [Arturo] Vidal, there are so many players we cannot just focus on one player. We know we have to play against 11 of them."
The fixture is a repeat of the 2009 and 2011 finals in which Barcelona triumphed both times under now-Manchester City manager Pep Guardiola, and Solskjaer will be hoping his side can earn a different result at Old Trafford.