The world number one will be overwhelming favourite to defeat semi-final opponent Denis Shapovalov, the Canadian player he has already beaten six times out of six.
With his 40th birthday in just five weeks' time, there will be doubts over his future in a sport where he is an eight-time Wimbledon winner and 20-time Grand Slam champion.
'Still not hundred per cent convinced': Roger Federer cautious as Wimbledon welcomes back capacity crowds
From Tuesday's start of the women's quarter-finals until Sunday's men's final, organisers can drop the 50% capacity rule which has been enforced since the start of the tournament.
All week at the All England Club, nurses, health staff as well as the developers of coronavirus vaccines have been honoured in the Royal Box on Centre Court.
Serena, a seven-time Wimbledon champion, is still one shy of Margaret Court's Grand Slam singles record of 24.
Ashleigh Barty was first ear-marked as a potential force on grass after winning the 2011 junior Wimbledon title aged 15.
Nadal, the 17-time major winner, has not got past the fourth round since finishing runner-up to Novak Djokovic in 2011.
Murray was playing only his second match after 11 months on the sidelines with a hip injury that required surgery in January.
Novak Djokovic hasn't earned a major title since completing his career Grand Slam by winning the 2016 French Open.
Garbine Muguruza 's victory over Venus, combined with her win against Serena in last year's French Open final, made the Spaniard the only woman to defeat each Williams sister in a Grand Slam.