First-half goals from Tim Matavz and Jeremain Lens set PSV on their way as the Eindhoven club sought to bounce back from last week's shock 3-1 home loss to Zwolle.
Heracles halved the deficit just after the hour-mark through Everton but that just served to spark PSV back into life as they responded with three goals in quick succession.
Georgino Wijnaldum made it 3-1 in the 66th minute, Dries Mertens added a fourth in the 72nd minute and then Wijnaldum completed the scoring with his second four minutes later.
PSV are now two points clear of second-placed FC Twente, who are away to fourth-placed Feyenoord tomorrow.
Seventh-placed ADO Den Haag will be disappointed not to have taken three points from the visit of relegation-battling Roda JC as they twice led and boasted a man advantage for almost the entire second half only to have to settle for a 2-2 draw.
Mike van Duinen put draw specialists ADO ahead in the 14th minute but they were pegged back through Mikolaj Lebedynski's equaliser on the stroke of half-time.
Roda were then reduced to 10 men four minutes after the break when Sanharib Malki was given his marching orders, and ADO looked to have made their extra man count when Danny Holla slotted home a 78th-minute penalty.
However, ADO lost their numerical advantage and their lead with three minutes to go when Vito Wormgoor was sent off for hand ball inside the area, conceding a penalty in the process.
ADO goalkeeper Gino Coutinho managed to turn Mark-Jan Fledderus' spot-kick onto the post, but the rebound was slotted home by the Roda midfielder to leave the home side with their 10th draw in 20 Eredivisie matches this season.
Elsewhere, Zwolle were almost brought crashing back to earth following their PSV upset as they trailed 1-0 at home to Heerenveen heading into the final six minutes, but substitute Denni Avdic cancelled out Alfred Finnbogason's 46th-minute opener to salvage a draw.
NAC Breda, meanwhile, beat RKC Waalwijk 4-0 away with Danny Verbeek (56 minutes), Jordy Buijs (58), Alex Schalk (80) and Eric Botteghin (90) the men on the scoresheet.