As a starting point, we can identify all cities that fall within that overlap:
In[7]:= jackson =
GeoNearest["City",
Entity["City", {"Jackson", "Mississippi", "UnitedStates"}], {All,
Quantity[115, "Miles"]}, DistanceFunction -> "Boundary"];
In[9]:= memphis =
GeoNearest["City",
Entity["City", {"Memphis", "Tennessee", "UnitedStates"}], {All,
Quantity[98, "Miles"]}, DistanceFunction -> "Boundary"];
In[11]:= Intersection[jackson, memphis]
Out[11]= {Entity["City", {"Beulah", "Mississippi", "UnitedStates"}],
Entity["City", {"BigCreek", "Mississippi", "UnitedStates"}],
Entity["City", {"Boyle", "Mississippi", "UnitedStates"}],
Entity["City", {"CalhounCity", "Mississippi", "UnitedStates"}],
Entity["City", {"Charleston", "Mississippi", "UnitedStates"}],
Entity["City", {"Cleveland", "Mississippi", "UnitedStates"}],
Entity["City", {"Coffeeville", "Mississippi", "UnitedStates"}],
Entity["City", {"Derma", "Mississippi", "UnitedStates"}],
Entity["City", {"Doddsville", "Mississippi", "UnitedStates"}],
Entity["City", {"Drew", "Mississippi", "UnitedStates"}],
Entity["City", {"DuckHill", "Mississippi", "UnitedStates"}],
Entity["City", {"Glendora", "Mississippi", "UnitedStates"}],
Entity["City", {"Grenada", "Mississippi", "UnitedStates"}],
Entity["City", {"Gunnison", "Mississippi", "UnitedStates"}],
Entity["City", {"Mantee", "Mississippi", "UnitedStates"}],
Entity["City", {"Merigold", "Mississippi", "UnitedStates"}],
Entity["City", {"MoundBayou", "Mississippi", "UnitedStates"}],
Entity["City", {"Oakland", "Mississippi", "UnitedStates"}],
Entity["City", {"Pace", "Mississippi", "UnitedStates"}],
Entity["City", {"Pittsboro", "Mississippi", "UnitedStates"}],
Entity["City", {"Renova", "Mississippi", "UnitedStates"}],
Entity["City", {"Rosedale", "Mississippi", "UnitedStates"}],
Entity["City", {"Ruleville", "Mississippi", "UnitedStates"}],
Entity["City", {"Schlater", "Mississippi", "UnitedStates"}],
Entity["City", {"Shelby", "Mississippi", "UnitedStates"}],
Entity["City", {"SlateSprings", "Mississippi", "UnitedStates"}],
Entity["City", {"Sumner", "Mississippi", "UnitedStates"}],
Entity["City", {"Tillatoba", "Mississippi", "UnitedStates"}],
Entity["City", {"Tutwiler", "Mississippi", "UnitedStates"}],
Entity["City", {"Vardaman", "Mississippi", "UnitedStates"}],
Entity["City", {"Webb", "Mississippi", "UnitedStates"}],
Entity["City", {"Winstonville", "Mississippi", "UnitedStates"}],
Entity["City", {"Woodland", "Mississippi", "UnitedStates"}]}
Depending on the curveature of the roads, any of these is a possibility.
W|A estimates that the driving distance from Derma to Jackson is 146.9 miles, so the GeoDisk/GeoNearest methods are probably inadequite for this task, unless the XKCD sign is intended to be for pilots. Perhaps this will be a nice jumping off point for someone else?