The setting of Serena by Ron Rash is the Appalachians, in Tennessee and North Carolina. Specifically, the setting is the mountains which will one day become the Smoky Mountain National Park. The time period is the 1930s, which is of course known as being the time of the Great Depression. Both of these factors, time and place, make a significant contribution to the story's plot and themes.
The Great Depression was a time of have-nothings and have-nots. Those who had nothing were always scrambling just to survive, which is the part of the Great Depression depicted by Rachel Harmon's story line. Those who had everything were willing to be philanthropists, as depicted by Rockefeller's willingness to contribute so much money to create the national park. In between are those like Pemberton and Serena who have some, even have enough, but are never content and want more. They take advantage of both the rich and the poor to advance their own cause.
The setting is essentially the wilderness of the mountains. There is a reason why people and the government were trying hard to protect this land. People like Pemberton (and there were more than thirty logging companies doing the same kinds of things all over the mountains) were acting ruthless and murderous in their pursuit of their fortunes.
The Appalachians are known as a place of some mystery and superstition (even today), which is one of the reasons Serena fits in so easily. Her connection to nature is a bit uncanny, though not in a pleasant or magical way. She kills a bear, she trains an eagle, and she trains that eagle to do even more killing for her. In keeping with the mystique of the mountain, a panther is rumored to be roaming around, though the hard reality is that there have been no actual physical signs of such a creature for years. The panther, even though it is non-existent, provides a specter of unknown but anticipated fear throughout the novel.
This is a relatively lawless land and killing of every kind is rampant. Men are killing trees as well as the creatures around them, some for food and some because they pose a threat to the operation. Humans are killing other humans, both literally and figuratively (as in the case of Rachel and Jacob) and their motives, like the work they are doing, is a blight on the beautiful nature surrounding them.
At one point in the novel, Pemberton notices
an immense chestnut tree rising out of the woods behind the sawmill. An orange growth furred the bark, and the upper branches were withered, unleafed.
"Good that it takes them years to dies completely," Serena said.
There is a slow-growing blight in the trees, and this feature of the setting also serves as a significant foreshadowing of the slow-growing blight in the primary players in the novel, Pemberton and Serena.
In all, the lawlessness, selfishness and greed of Pemberton and his wife are able to come to full fruition because of when and where they live. The setting then becomes a significant factor in this particular novel.
[On a personal note, I see the Smoky Mountains from my porch every day, and they are truly beautiful. They have recovered from those awful days of greed and exploitation and are now protected for all to enjoy.]