The clubs have met 27 times in the past but this will be the first time they have clashed in the Eredivisie.
Heracles are on a three-match winning run, which has seen them move out of the bottom three despite losing their first seven league games this season.
Dordrecht, on the other hand, have lost each of their last 10 and are in real danger of being cut adrift. They already sit eight points behind second-bottom NAC Breda.
NAC halted a run of four straight defeats last time out, winning 1-0 at previously in-form Cambuur thanks to Erik Falkenburg's first-half strike.
They will aim to build on that success in a home match against Heerenveen on Saturday.
At the other end of the table, leaders PSV will welcome Twente to Eindhoven on Sunday having faced Dinamo Moscow in the UEFA Europa League on Thursday, while second-placed Ajax host Utrecht following a routine 4-0 UEFA Champions League win over APOEL on Wednesday.
Frank de Boer will be without Kolbeinn Sigthorsson, however, as the Icelandic striker suffered an ankle injury against Willem II last weekend and is expected to be out until the new year.
Nevertheless, Sigthorsson signed a new contract earlier this week, running until the end of the 2015-16 season.
Third plays fourth in Rotterdam on Sunday as Feyenoord, another side in Europa League action on Thursday, host AZ.
The teams are locked on 27 points heading into the weekend, six behind Ajax, and there appears little to choose between them with both having won four of their previous five league matches.
Feyenoord's two games against AZ last season finished all-square.
Should there be a winner in that game, PEC Zwolle can climb above the loser with a third straight league win away at Willem II on Saturday.
Michiel Kramer took his league-leading goalscoring tally to 11 in ADO Den Haag's defeat to PEC last time out and will hope to be among the goals once more as his team have an opportunity to leapfrog Excelsior, and climb out of the drop zone, when the teams meet on Saturday.
Elsewhere, Go Ahead Eagles host Cambuur on Saturday while Vitesse could climb above Groningen with victory in Sunday's meeting.