Place foil in a 9x13 pan and lightly grease with cooking spray; set aside.
Combine sugar, melted butter, evaporated milk, pumpkin, and karo syrup in a large pot. Heat over medium-high until mixture comes to a boil, stirring continually. Continue to stir for 12 more minutes to cook.
Remove from heat and add vanilla, white chocolate chips, and marshmallow fluff. Mix well to combine.
Pour mixture into prepared pan. Allow to cool for at least 2 hours before cutting.