Having bowed out in the final four of this year's Carabao Cup and FA Cup, the Red Devils are looking to go one better when they return to Stadion Koln to take on the in-form Spaniards.
Sevilla's quarter-final victory against Wolves was more one-sided than the 1-0 scoreline suggests, while United have had an additional day's rest after winning by the same scoreline against FC Copenhagen in extra time.
Solskjaer's first piece of silverware in the hotseat would be a big moment on the back of their third-placed Premier League finish, with the 1999 treble hero underlining the fact that semi-finals appearances are not enough.
"It's like a European Championships or a World Cup – you don't get a second chance, there is no tomorrow," Solskjaer told MUTV.
"You just know that you have to leave everything on that pitch, which is for me fine.
"It's a different set-up than we're used to. We're used to home and away, but for me this is the best scenario that we can finish this tournament.
"All the teams have played many games anyway. but now it's who is the mentally strongest?
"Who looks at the opponent and he's tired, I feel tired but he's more tired than me.
"You've got to be strong mentally, concentrated, focused and any of these games can be decided, will be decided, on marginal decisions or finishing.
"So, we've just got to keep them focused and with the right attitude."
A number of those in United's squad were part of the side dumped out of the Champions League by Sevilla in March 2018, when a brace from substitute Wissam Ben Yedder sealed a shock 2-1 last-16 win at Old Trafford.
Solskjaer is plotting a own revenge mission of his own, having seen his Europa League dreams extinguished by the Andalusians when managing in his homeland.
"I was the manager of Molde," he said. "We lost against them in 2016 I think it was.
"They beat us 3-0 away, we beat them 1-0 in Molde, so I've got something that I need to sort out with them."