Ireland, the Grand Slam champions, take on Australia, Wales face Argentina while Scotland take on Canada and Italy visit Japan.
And here we break down each of the team selections and preview the four clashes that will be packed full of Guinness PRO14 talent.
Ospreys’ new signing George North will return to the wing this weekend after lining up in the centres last weekend against the Springboks.
He replaces Scarlets star Steff Evans after the latter’s injury – but there are a whole host of Scarlets drafted into the side that will be captained by Cory Hill.
Gareth Davies and Rhys Patchell were the half-backs for the Scarlets’ run to the Guinness PRO14 final and are reunited by Warren Gatland while Hadleigh Parkes and Scott Williams also team up in midfield.
A big congratulations to Ospreys players Adam Beard, Owen Watkin and next season’s new faces Scott Williams, George North and Aled Davies!
— Ospreys (@ospreys) June 6, 2018
Elsewhere James Davies, a turnover machine in the Guinness PRO14, gets the start at openside while Wyn Jones comes into the front to take on a Pumas side who will be tough to beat on home soil and with the Jaguares in such fine form in Super Rugby.
Edinburgh flanker Jamie Ritchie has been rewarded for his superb domestic form with a first international start on Saturday for Scotland.
The versatile back rower will make his debut in the No.7 jersey alongside his Edinburgh teammate Magnus Bradbury who is at blindside and No.8 David Denton.
Ritchie’s teammate Lewis Carmichael could also make his bow if he comes off the bench along with Glasgow Warriors fly-half Adam Hastings.
ICYMI ⏪ | Jamie Ritchie is set to earn his first cap in Scotland’s summer tour opener against Canada. 💪
Read the rest of the team news ahead of this weekend’s clash 🇨🇦🏴 #AsOne
— Edinburgh Rugby (@EdinburghRugby) June 6, 2018
Ruaridh Jackson gets the nod at No.10 for the Scots who are without the injured Stuart McInally so Grant Gilchrist will skipper from the second row in his stead.
Blair Kinghorn – the top metre maker in the Guinness PRO14 this past season – will also make his first international start at full-back with Stuart Hogg rested.
Ireland take their 12-game winning run to Brisbane on Saturday to take on the Wallabies and the headline news is the inclusion of Joey Carbery at fly-half.
Carbery starts but a number of Leinster stars are rested following their exertions in completing a Guinness PRO14 and European double.
Jonathan Sexton is on the bench as are Cian Healy, Sean Cronin and Jordan Larmour.
— Irish Rugby (@IrishRugby) June 7, 2018
Rory Best’s injury absence means Munster’s Peter O’Mahony takes over as captain in a back row that includes his provincial teammate CJ Stander and Ulster-bound Jordi Murphy.
A new-look front row sees Jack McGrath pack down with Rob Herring and John Ryan while Iain Henderson and James Ryan remain the second-row pairing.
Robbie Henshaw and Bundee Aki reunite in midfield while Rob Kearney is at full-back with Keith Earls and Jacob Stockdale either side.
Tiziano Pasquali earns his first Italy start on Saturday against Japan after his fine showings in Benetton’s record-breaking Guinness PRO14 season.
Pasquali starts in the front row in pack that includes five different Benetton players but is captained by hooker Leonardo Ghiraldini.
— Italrugby (@Federugby) June 7, 2018
While Benetton dominate the pack, Zebre hold sway in the back line with the half-back Marcello Violi joining Tommaso Castello at inside centre, Mattia Bellini on the wing and breakout star of the season Matteo Minozzi retained at full-back.
Elsewhere Tommaso Allan gets the nod at No.10 while Seb Negri joins Giovanni Licata and Abraham Steyn in an energetic back row.
Furthermore uncapped front rower Giosuè Zilocchi could make his debut if called off the bench in the clash with Japan.