Sligo Rovers begin the defence of the FAI Ford Cup with a home tie against FAI Junior Cup champions Pike Rovers at the Showgrounds, kick-off 7.45pm.
Sligo boss Paul Cook said that the Limerick side has his full respect, particularly after their cup victory over St Michael's of Tipperary last month.
The Bit o' Red, who are second in the Airtricity League, will be without the injured Joseph Ndo (calf).
Pike Rovers reached this stage by seeing off Avondale United of the Munster Senior League in a replay.
Last season's runners up and league champions Shamrock Rovers launch their campaign to go one better against Athlone Town at Tallaght Stadium, kick-off 8pm.
Rovers boss Michael O'Neill admitted that last season's defeat to Sligo will spur on his side this time.
O'Neill said: 'It's a break from the league, which the lads will welcome because of the amount of matches we have had recently. But that doesn't make it any less of a big game for us. After just missing out at the final last year, we'll want to go one better this year.
'We'll approach the game in a professional manner and do what we need to do to hopefully get the win. While we'll no doubt be favourites, we'll be giving Athlone the respect they deserve in this tie.'
Although there are doubts over Alan Mannus (shoulder) and Gary Twigg (dead leg), O'Neill expects both men to be fit.
The visitors have several injury worries with Gary Higgins (hamstring), Brendan Daly (back), Michael Schlingermann (knee), Kevin Williamson (knee) and Eoin Monaghan (groin) struggling.
As all St Patrick's Athletic fans know, it is 50 years since they last won the FAI Cup and the quest to end that wait begins against Crumlin United at Richmond Park, kick-off 7.45pm.
The Leinster Senior League side were drawn as the home side, but their Pearse Park ground could not accommodate the crowd and the game has been switched.
Crumlin have knocked out Shelbourne and Waterford in recent years and St Pat's' boss Pete Mahon is well aware of the threat his side will face.
Mahon said: 'I know how much it means to everybody, but this game is a potential banana skin for us and we will treat Crumlin with a lot of respect.
'We have a tough schedule of games coming up, so we will make a few changes and try to get people game time, but this is a game, like all games, that we want to win.
'Crumlin have a good record in this competition and we are well aware that they have knocked out Shelbourne and Waterford United in recent seasons.
'We came close to winning the trophy last season getting to a replay in the semi-final, but we want to win it this season and to do that we have to start with getting a victory over Crumlin United.'
Mahon will once again be without Conor Kenna (knee), but Neil Harney and Anto Murphy are fit again.
Crumlin, who beat St Michael's to reach the third round, finished mid-table in the LSL Senior Division in the past season.
Derry City put their title challenge on hold for the evening as they travel south to face Wexford Youths at Ferrycarrig Park, kick-off 8pm.
Stephen Kenny has a full squad to choose from following Monday's 6-0 thumping of Galway United.
'We are playing well and scoring goals, but with an FAI Cup game away in Wexford we'll have to be at our best to win. We'll prepare well and make sure were ready,' said Kenny.
Anthony Russell is the only absentee for Youths who are promising to attack the Candystripes.
'Attack is the best form of defence and with this group of players it doesn't suit them not to stand off the ball. I think it leaves us exposed when we do that,' said manager Noel O'Connor.
For the fifth year in succession, Bohemians face an Intermediate side in the FAI Cup as Douglas Hall travel to Dalymount Park, kick-off 7.45pm.
The Gypsies won all four previous encounters with differing degrees of difficulty; Glenville and Mayfield United were thrashed, while Drogheda Town and Malahide United provided stiffer opposition.
Ollie Cahill (hamstring) and Mark Rossiter (hamstring) miss out again, but Barry Murphy (groin) could make a return.
Douglas Hall missed out on Munster Senior League glory when they lost to Rockmount in a league play-off. They beat Glebe North of the LSL to secure this glamour tie.
UCD face a potential tricky tie when they meet Cherry Orchard at Belfield, kick-off 7.45pm.
The Orchard, who switched the game to UCD, have just returned to the top flight in the LSL at the first time of asking, as well as reaching the final of the FAI Intermediate Cup.
'This is the FAI Cup and it is a massive opportunity for us to progress on in the competition,' said UCD manager Martin Russell.
'We have watched Cherry Orchard three times and although for once we may be considered the favourites, we are going to show them the respect that they deserve for reaching this stage.
'We will focussing on producing a good display and will hope that will be enough to see us to the next round.'
The Students will be without Robbie Creevy (ankle) and top scorer Graham Rusk (foot) is a doubt.
Premier Division strugglers Drogheda United take on Mervue United at Hunky Dorys Park, kick-off 7.45pm.
The Louth outfit will want to put their disappointing league campaign to one side and progress in a competition they won in 2005.
'The cup is always a nice distraction, but one thing we will not be doing is underestimating Mervue, said boss Mick Cooke.
'I obviously played against them last season and they are certainly capable of putting it up to us. They beat me at Monaghan and effectively ended our promotion hopes, so I know what they are capable of.
'This is a competition that I want to compete in, so I will be putting out my strongest team.'
Jack Flynn is missing for the game against the Galway side, who sit in mid-table in the First Division and will be no pushovers.
Waterford United begin life under are caretaker manager Paul O'Brien with a home tie against New Ross Celtic at the RSC, kick-off 7.45pm.
Stephen Henderson was fired last week following a poor run of results that has seen the Blues slip down the table.
Brian Nolan is a slight doubt with an ankle problem and Michael Rafter has had his contract terminated by mutual consent.
New Ross thrashed Munster Senior League champions Rockmount 4-1 in the second round.
Flancare Park hosts the all-First Division clash of Longford Town and Finn Harps, kick-off 8pm.
Both sides have injury problems, but with four players missing, Longford are the hardest hit.
Former Manchester United winger Keith Gillespie (hamstring) is among the absentees, along with Michael Lee (groin), Jacques Morley (ankle) and Graham Dowling (knee).
Finn Harps will be without Gary Whoriskey (knee), Conor O’Grady (ankle), while James Doherty could feature at some stage.
'It's a game we're capable of winning if we keep on playing and improving from our recent performances. A good cup run would do us the world of good and give us something to build on,' said Harps manager Peter Hutton.
Cork City expect to field a strong side when they take on neighbours Midleton at Knockgriffin Park, kick-off 7.45pm.
'I will bring one or two players in, but it won't change the strength of the team. There is no way we will be going to Midleton with a weakened team,' said boss Tommy Dunne.
Davin O'Neill is the only absentee as he is getting married and will miss the next three games.
In-form Monaghan United will host Munster Senior League side Everton at Gortakeegan, kick-off 8pm.
Roddy Collins is another manager who will be showing respect to his lower-ranked opponents.
'From my time in Cork, I am familiar with Everton. They have a good history, especially in underage football,' said Collins.
'Like all managers, I detest the title of "favourites". Cup competitions are littered with the skeletons of such creatures. Cup ties always have their own magic and can throw up the occasional surprise.'
Drom is the venue as the Airtricity League's bottom side, Salthill Devon, take on Sheriff YC of the AUL, kick-off 7.45pm.
The Dubliners have three futsal internationals in their squad and will cause problems for Paul McGee's side.
