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Preheat oven to 425°F. Line a large rimmed baking sheet with parchment paper. Trim ends of spaghetti squash; cut crosswise into 4 equal rounds (about 1½ inches thick). Scoop out and discard seeds.
Combine 2 tablespoons oil and ½ teaspoon each garlic powder and onion powder in a small bowl. Arrange the squash rounds on the prepared baking sheet; drizzle with 1 tablespoon of the oil mixture. Roast until tender, 30 to 35 minutes. Remove the squash from the oven; reduce oven temperature to 375°F.
Meanwhile, combine artichokes, spinach, ⅓ cup cream cheese, ¼ cup each milk and Parmesan, 1 teaspoon basil, ½ teaspoon each crushed red pepper and lemon zest and the remaining ½ teaspoon each garlic powder and onion powder in a medium bowl; stir until thoroughly mixed and creamy.
Shred the centers of the squash rounds into long strands while keeping the rounds intact. Drizzle the remaining 1 tablespoon oil mixture over the shredded squash nests; sprinkle with ⅛ teaspoon salt.
Divide the vegetable mixture among the squash nests. Top with ¼ cup mozzarella. Bake until the mozzarella is melted, about 5 minutes. Sprinkle with the remaining ⅛ teaspoon salt. Garnish with crushed red pepper, if desired.