I really Have to wonder why a Crossover universe between EqG and S.T.A.L.K.E.R never dawned upon Anyone? There's already Fallout: Equestria so why not a, "S.T.A.L.K.E.R: Shadow of Canterlot"?
We could use the phenomena of Equestrian Magic and Magical items being dumped into the Human World to create the setting. Where Fallout Equestria uses Megaspells to create the wasteland, A Huge Cataclysmic discharge of Magic would create the EqG version of "The Zone". Heck, it could even be the result of megaspell magic or a megaspell ending up in the Human world and going off in Canterlot City. Creating a magical Exclusion zone similar to Chernobyl and Fukushima's exclusion zones. But with magic in place of radiation. Said magic would create The Anomalies said said Equestrian items serving as the Artifacts.
Like the Zone from the games, This version of the Zone would also be slowly expanding. The Mane 7, the holders of the Geodes of Harmony serving as this universe's version of the Common Consciousness or C-Consciousness. Halting the zone's expansion and being situated right at the being located in the Epicenter of the Zone: Canterlot Highschool.
As a result of the Discharge, Magic now freely flows into the Human world and Flora and Fauna from Equestria have now entered the Human world and radically alters the Ecosystem within it.
From Time to time, Large discharges of Equestrian magic would be released into the zone. Replenishing it's artifacts and providing a constant supply of magic within the Zone. Said discharges resembling the Emissions or Blowouts from the games. Being this awesome spectacle to those in the zone and beyond. Being seen for miles.
It's also meant to be the opposite of Fallout: Equestria's Setting. Being overgrown and reclaimed by nature instead of a bleak wasteland and being in an exclusion zone instead of an entire post apocalyptic world.
As for the Location of the Zone, It's in between the Border of Canada and the US and it's uncomfortably close to Seattle and Vancouver.