The five-time Ballon d'Or winner has been in typically sublime form for Barcelona this season and he dragged a ragged Argentina to qualification for Russia 2018 by scoring a sensational hat-trick away to Ecuador last October.
The Albiceleste fell at the final hurdle as Germany prevailed 1-0 after extra-time in the 2014 decider and anticipation over what Messi might achieve in the final World Cup of his peak years is palpable.
The 30-year-old moving to Catalonia in his youth has been a factor in fans from his homeland not always taking him to their hearts as they have other Argentina heroes but he is now indisputably the main man carrying all hopes of glory – something Sampaoli illustrated after confirming the forward's fitness at a pre-match news conference in Madrid.
"It is impossible to teach something to Messi. His level is unattainable. You have to understand Messi, not teach him," he said.
"In training you have to try to cause situations in which his comfort will be optimal. From there, you have to build a team related to this story.
"You have to learn from these kind of players that come around every so often. You have to learn how to go with them, not even in coaching terms, but in the sense of how to bring harmony to him, surrounding him with the right atmosphere.
"In that sense, Leo is very open to interact a lot with what he feels inside the pitch. The interpretation of a player with such a capacity inside the pitch gives the coach a better perspective of what is coming because his lenses are probably much more developed than ours.
"Luckily, the dialogue with him is very constant. I always see him at a high level of compromise with the national team and its wishes. We will go through this together."
Messi will square off against Spain and Real Madrid captain Sergio Ramos, a clash that could contradict the match's friendly status.
Nevertheless, the occasionally feisty nature of their Clasico showdowns does not give Sampaoli any cause for concern over Messi's fitness.
"They are two winners and I don't care how Ramos defends against Messi," he added. "Ramos is a great player for Real Madrid and the Spanish national team.
"If there was any risk [in his condition], Leo would have said. He told us before the last friendly.
"He was tested yesterday and tried again today. If he continues like this, he will have no problems playing."