In the West, league leaders Aberavon host second-place Llandovery knowing a win or a draw will see them end on top of the pile.
Meanwhile, in the East, Newport host Ebbw Vale safe in the knowledge a win will see them finish ahead of second-place Cardiff.
The Drovers are the only team to have beaten Aberavon to date, their 24-18 victory at the Talbot Athletic Ground coming in the fifth round of matches on October 16.
The only defeat suffered by Llandovery was a shock 25-19 reversal at home to Bridgend.
With a two-point gap between the two teams, there is everything to play for to earn the bragging rights of finishing on top of the table.
The first four teams go through to the knock-out phase in the New Year, with the top two taking home advantage.
“We’re in a good run of form and we’re unbeaten away from home. It would be great to finish as top dogs, but we know how strong Llandovery can be,” said Aberavon head coach Jason Hyatt.
“We’ve still got a number of injuries around the place, but Aled Thomas should be fit to return when we get into the proper league programme.
“It has been great being able to blood some youngsters and we’re in a good place at the moment.”
In the other games in the West, Carmarthen Quins welcome arch-rivals Llanelli and Swansea host Bridgend.
While Llanelli cannot reach the next phase, if Bridgend can win at St Helen’s they could clinch the fourth spot.
In the East, Newport will be targeting a double over Gwent rivals Ebbw Vale.
The Steelmen were beaten 44-17 at home when the two sides met earlier in the competition and have lost their last seven in a row after a promising start that saw them beat Merthyr and Pontypridd.
They cannot make the top four, but for Newport there will be twin goals.
They will want to rectify the defeat they suffered in their last home outing against RGC and also deny Cardiff top spot.
Cardiff are two points adrift and welcome Merthyr to the Arms Park for a game from which the Ironmen need to get at least a point to be guaranteed a top-four finish.
After their crushing win at home over Pontypridd two weeks ago, they then tumbled to a big defeat to Newport.
Cardiff, meanwhile, also lost at home to Newport but have since picked up impressive bonus-point victories over Ebbw Vale and Pontypridd.
Justin Burnell’s Pontypridd head north to face RGC 1404 in another crucial battle for a top-four finish.
The Gogs are two points behind Merthyr and two ahead of Pontypridd after their impressive recent run of a win at home over Merthyr and then away triumphs against Newport and Ebbw Vale.
WRU Premiership Cup fixtures – Saturday, November 27
East
Cardiff vs Merthyr
Newport vs Ebbw Vale
RGC vs Pontypridd
West
Carmarthen Quins vs Llanelli
Llandovery vs Aberavon
Swansea vs Bridgend
