Pep Guardiola's injury-hit Bayern struggled immensely in Portugal, falling 2-0 down within the first 10 minutes thanks to a Ricardo Quaresma double, and eventually lost 3-1.
The Bundesliga pacesetters are now facing the possibility of missing out on a fourth successive Champions League semi-final appearance and history will not provide much inspiration.
The Bavarian giants have chased a two-goal first leg deficit four times in UEFA competition and lost every single tie.
"We know it's the biggest game of the season," Neuer said. "Every one of us will do everything we can to make it a good performance."
And Guardiola echoed his goalkeeper's sentiments, saying: "It's a final. We need a great performance.
"It'll be tough, but we'll give it a go. I have lots of faith in my players."
Despite a lengthy injury list – including the likes of Franck Ribery, David Alaba and Arjen Robben – Bayern warmed up for Tuesday's clash with a 2-0 triumph at Hoffenheim on Sunday, edging closer to a 25th Bundesliga title.
Bayern can take solace from their home form in this year's competition, emerging victorious in all four of their outings at the Allianz Arena and scoring 13 goals in the process.
Bastian Schweinsteiger may be able to feature, but Bayern's list of absentees still looks set to cause havoc with Guardiola's team selection.
Bayern will continue to be without Robben (abdominal muscle), Ribery (ankle), Tom Starke (ankle), Mehdi Benatia (thigh) and Javi Martinez (knee), while Jerome Boateng, Juan Bernat, Philipp Lahm and Neuer are just a booking away from a suspension.
Porto are under no illusions as to the pressure they are likely to come under in Munich, however, with Yacine Brahimi expecting Bayern to ask serious questions of Julen Lopetegui's defence regardless of their depleted numbers.
"It was an exceptional display [in Porto]," he said. "We couldn't have dreamed of a better result than 3-1, but we've still got an away game to play and it will be very, very difficult.
"Over there we need to play the way we did [in the first leg] – that is to play our game and play normally. We'll have to defend very well and be strong as a team."
Porto's chances of reaching a first Champions League semi since their triumphant 2003-04 campaign will not be helped by suspensions for full-backs Danilo and Alex Sandro, while Cristian Tello missed Saturday's 1-0 defeat of Academica with a thigh problem.
