Preheat the oven to 375 degrees F (190 degrees C). Poke 8 to 10 holes in the spaghetti squash; place whole in a baking pan.
Bake in the preheated oven until squash is easily pierced with a knife, about 25 minutes. Remove and let cool until easily handled.
Cut squash in half; remove seeds and ribs. Place squash halves facedown in a baking dish with a little bit of water and cover with foil. Bake until you can pull the sides away easily with a fork, about 25 minutes more.
Meanwhile, heat a medium skillet over medium-high heat. Cook and stir beef in the hot skillet until browned and crumbly, 5 to 7 minutes. Drain and discard grease. Set beef aside.
Heat a large, deep skillet over medium-low heat. Add olive oil, yellow squash, zucchini, bell pepper, onion, Italian seasoning, basil, black pepper, oregano, garlic powder, thyme, and red pepper flakes. Cook and stir until vegetables are tender, about 10 minutes. Pour in tomato sauce and simmer until heated through, adding the beef halfway through, about 10 minutes more.
Turn spaghetti squash face-up; shred the sides from the center out with a fork. Scoop "spaghetti" from squash onto serving plates. Flatten and top with the sauce.