For the shrimp and fish: Attach a deep-fry thermometer to the side of a heavy wide pot. Fill the pot 2 inches full with the oil. Heat to 350 degrees F over medium heat.
Whisk the garlic powder, cayenne, thyme, salt and pepper in a large bowl. Toss the shrimp and tilapia with the spice mixture and stir to coat. Pour the milk over the fish and shrimp.
Whisk the flour and cornmeal in a baking dish. Working in batches, toss the shrimp and tilapia in the flour mixture and then carefully place into the pot. Fry the shrimp and tilapia, stirring occasionally, until golden brown and just cooked through, about 4 minutes each batch. Transfer the shrimp and tilapia to paper towels to drain. Sprinkle the shrimp and tilapia with salt immediately after frying.
For the creamy garlic spread: Blend the mayo, garlic, zest and lemon juice in a bowl.
For the po' boys: Cut open the baguettes longwise, three-quarters of the way through the bread. Spread the cut sides with the creamy garlic spread. Divide the shrimp and tilapia among the baguettes and top with lettuce, tomato and hot sauce, if using.