The destination of the trophy in the much-anticipated meeting of record five-time winners Toulouse and four-time champions Leinster hinges largely, MacNeill says, on who wins the battle of the halfbacks.
Toulouse have the A-List duo of Antoine Dupont and Romain Ntamack at scrum-half and fly-half respectively up against the "outstanding" Jamison Gibson-Park and the inconsistent Byrne.
Byrne, 29, like many who challenged the now retired Sexton both at province and international level came off second best and it clearly had an impact.
"Sexton cast a very large shadow and it has not been easy for Byrne to replicate that or impose himself in such a short space of time," MacNeill told AFP by phone.
Whilst the likes of Ian Madigan and Joey Carbery left to get more game time, Byrne stuck it out but seemingly to his detriment as by last year's Rugby World Cup he had slipped from Ireland's second choice to third choice fly-half.
That is why MacNeill says Saturday's match at the Tottenham Hotspur Stadium is absolutely crucial for Byrne.
It offers him the opportunity to wrest the Ireland shirt back off the younger Jack Crowley, who was first choice during Ireland's Six Nations title-winning campaign this year.
The 37-time capped MacNeill - a member of the 1982 and 1985 Triple Crown-winning teams - says it depends on which Byrne turns up.
Will it be, says MacNeill, the one who inspired Leinster to trounce two-time defending champions La Rochelle in the quarter-finals?
Or will it be the playmaker who went into his shell as big leads slipped away against both La Rochelle in last year's final - Leinster led 17-0 after 12 minutes but lost 27-26 - and Northampton in this season's semi-final when they had a 15-3 lead at the break only to scrape home 20-17?
"It is a pivotal moment for Byrne and his career," said MacNeill.
"He has the chance to make a permanent mark or he can be left to lick his wounds.
"It may decide who wears the No. 10 shirt for Leinster in the years to come, him or Sam Prendergast," added the 65-year-old former Leinster fullback.
'Intelligent options'
MacNeill, who was also capped three times by the British and Irish Lions, says Byrne has to do what he did against La Rochelle in the 40-13 quarter-final victory.
"Byrne has to kick his penalties to keep the scoreboard ticking over and also drive his team forward," said MacNeill.
"He has to repeat what he did against La Rochelle and failed to do against Northampton, ease the creeping fear round the ground and amongst his teammates."
MacNeill says the uncertainty surrounding Byrne is in stark contrast to that of Ntamack, who is back in prime form after injury robbed him of appearing at the World Cup.
"He is up against Ntamack who is a seasoned international with no question marks over his place in the team either at club or country level," said MacNeill.
"Toulouse to my mind are favourites especially if Dupont and Ntamack are allowed to set the pace.
"Leinster will have some hope of competing if Gibson-Park is at his best and gets some rhythm.
"Gibson-Park and Byrne have to go in there from the start and impose themselves."
For MacNeill, Dupont, who is back from sevens duty with France, is "at the top of his game and called all the shots in their semi-final win over Harlequins" but Gibson-Park too is a formidable operator.
"He is absolutely key to Ireland and Leinster's success," said MacNeill.
"He brings pace and rhythm to the game and he generally takes the intelligent options, he finds space.
"Jamison has stepped up and filled a vacuum in the wake of Johnny Sexton's retirement.
"It is clear his teammates have as much respect for him as they did for Sexton."
"He is one of the most, if not the most, influential scrum-halves in the northern hemisphere."
