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Gather all ingredients. Grease a 9x13-inch baking dish.
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Spread panettone cubes on a baking sheet. Bake until dry, stirring twice, about 15 minutes. Panettone cubes will continue to dry as they cool. Transfer panettone cubes to the prepared baking dish.*
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Whisk together eggs, half-and-half, sugar, melted butter, vanilla, and salt in a large bowl. Pour over panettone cubes. Press down panettone cubes with the back of a spoon to submerge and soak in the custard mixture. Cover and chill at least 30 minutes and up to 2 hours.
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Preheat the oven to 350 degrees F (175 degrees C). Bake bread pudding in the preheated oven until puffed, golden brown, and a knife inserted in the center comes out clean, 40 to 45 minutes. (Internal temperature of bread pudding should be 160 to 175 degrees F (71 to 79 degrees C) .
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Dust with powdered sugar, if desired.