Federer's shock defeat to 12th seed Tomas Berdych in the quarter-finals on Wednesday has given a huge shot of adrenaline to the four remaining players in the men's singles draw as they bid to replace the Swiss star as Wimbledon champion.
The chief beneficiary of Federer's exit could be 2008 champion Nadal, who is desperate to regain the title he was unable to defend last year due to knee tendinitis.
French Open champion Nadal has shrugged off a knee problem that bothered him earlier in the tournament and was in fine form as he fought back from a set down to win his grudge match with long-time rival Robin Soderling in the last eight.
Next in Nadal's firing line is British fourth seed Murray, who defeated France's Jo-Wilfried Tsonga to book his place in the semi-finals, and the Spanish second seed plans to take the attack to an opponent who is sometimes more cautious than he should be in big matches.
"My game is try to play aggressive and the important thing is serve well," Nadal said.
"I am happy with how I'm playing, so I'm going to try to do my normal game. I don't want to change a lot of things.
"The styles of Murray and Soderling are completely different. But at the same time, I still have to play at my best level if I want to have a chance to win."
Murray is just two victories away from becoming the first British man to win Wimbledon since Fred Perry in 1936 and he looks capable of going all the way after dropping just one set en route to the last four.
The 23-year-old Scot, who was beaten by Andy Roddick at this stage last year, can take heart from his wins over Nadal at the US and Australian Opens and he won't fear the world number one on Centre Court.
"He would definitely be the favourite for the match with his results here the last few years," Murray said.
"But psychologically I need to believe that I can win the match. That's the most important thing.
"I know it's going to be an incredibly difficult match to win, but it's one I believe I can win if I play well."
In the other semi-final, Serbian third seed Novak Djokovic takes on Berdych.
Djokovic now has an excellent chance to reach a Grand Slam final for the first time since he won the 2008 Australian Open.
He made the semi-finals here in 2007, but was forced to retire due to back and foot injuries.
"This time I'm ready mentally and physically. Just barely waiting to get on the court," the world number three said.
"Playing a semi-final of any Grand Slam is a huge result. But having the opportunity to reach the final is even more encouraging, of course, and more challenging. I will definitely fight till the last moment."
Berdych reached his first Grand Slam semi-final at the French Open last month and is the first Czech to reach the Wimbledon last four since Ivan Lendl in 1990.
"He's a big server and he has powerful groundstrokes. His weapon is his forehand," Djokovic said.
"He has not much to lose. He's going to be motivated. So there's no favourites. But still, I would give everything to play in the Wimbledon final."
Djokovic won their two previous clashes in straight sets but Berdych said: "It's going to be everything different, playing the semi-finals of a Grand Slam. It's going to be a really, really tough one.
"Of course, you need to have some confidence to get to the semi-final, so it's going to be really the same for both of us. I'm looking forward to that match.
"We're going to see what Novak's going to do on the court. But the more important thing is how my game is going to be."