These two teams currently occupy 20th and 18th place in the standings respectively, albeit having avoided defeat in their last fixtures.
Match preview
Having only lost one of their last five fixtures in the Championship, Stoke may have hoped to have been further clear of the relegation zone at this stage.
However, avoiding defeats against a couple of their rivals has kept the Potters in a position where their fate remains very much in their own hands.
With three fixtures remaining, Stoke sit three points clear of the relegation zone ahead of games against Southampton and Bristol City which follow this one.
Holding a better goal difference than two of the three teams below them, Steven Schumacher knows that triumphing over his former club could prove to be the pivotal result.
On the flip side, though, Stoke face the possibility of ending the weekend in the bottom three if they suffer their 10th home league defeat of the campaign.
Plymouth have already parted ways with Schumacher's successor Ian Foster, yet it appears to be an inspired decision in the grand scheme of things.
Interim boss Neil Dewsnip has since guided the Pilgrims to seven points from three games, a run that has included a 1-0 victory over Leicester City.
With another of the points coming against relegation rivals Queens Park Rangers, Plymouth now sit in 18th spot, four points clear of the bottom three.
Dewsnip will back his side to get over the line against Millwall and Hull City, yet this fixture will be viewed as the ideal moment to avoid any concerns heading into the final two games of the season.
Stoke City Championship form:
L
W
D
D
L
D
Plymouth Argyle Championship form:
L
L
L
W
D
W
Team News
Schumacher is expected to tinker with his Stoke side, with Luke Cundle in contention for a recall at the expense of Lewis Baker.
Bae Jun-ho also seems likely to be restored in the final third, while Enda Stevens is an option at left-back ahead of Jordan Thompson.
Wouter Burger's place in the team is in doubt due to a knock from last weekend, but Lynden Gooch and Ryan Mmaee will miss out through injury.
As for Plymouth, Joe Edwards is expected to come back into the team at the expense of the injured Mickel Miller.
With Plymouth having over a week to prepare for this game after beating Leicester, no further alterations are likely.
Stoke City possible starting lineup:
Iversen; Wilmot, McNally, Rose, Thompson; Laurent, Burger; Leris, Cundle, Bae; Campbell
Plymouth Argyle possible starting lineup:
Cooper; Pleguezuelo, Scarr, Galloway; Edwards, Forshaw, Randell, Mumba; Whittaker, Bundu; Hardie
We say: Stoke City 1-1 Plymouth Argyle
This has the potential to be an extremely tense affair, one in which both sides may be focused on avoiding losing. With that in mind, do not be surprised to see a low-scoring draw play out in the Potteries.