Place flour and powdered sugar in large bowl. Cut in margarine until mixture resembles coarse crumbs. Press dough into the bottom and up the sides of a 9 inch deep dish pie plate.
Bake crust in the preheated oven for 20 minutes. Set aside to cool.
Place the cantaloupe in a medium saucepan over medium heat. In a 2 or 4 cup measuring cup, whisk together sugar, flour, cornstarch, and salt, and then stir into the cantaloupe. Cook and stir until mixture comes to a low boil and begins to thicken. Beat egg yolks and water together in a small bowl. Gradually stir in small amounts of cantaloupe mixture to prevent yolks from curdling. Pour yolk mixture back into pan and continue cooking for 2 minutes more. Remove from heat and set aside to cool. Once cooled slightly, pour into pre-baked, cooled pie shell.
In a bowl, cream together the Neufchatel cheese and sugar. Beat in milk and vanilla until smooth, then fold in thawed frozen whipped topping until well blended. Spread evenly over cantaloupe layer. Cover and refrigerate at least 2 hours before serving.