Bring a large pot of water to a boil. Cook the penne according to the package instructions until al dente. Reserve ½ cup of pasta water, drain the pasta, and set aside.
Heat the olive oil in a large skillet over medium-high heat. Add the chicken, season lightly, and cook for approximately 5–7 minutes, turning as needed, until the thickest pieces reach 165°F (74°C). Transfer to a clean plate.
Add the mushrooms and onion to the skillet. Cook for 5–7 minutes, stirring occasionally, until the mushroom moisture evaporates and the edges begin to brown.
Add the garlic and cook for 30 seconds, stirring constantly.
Add the asparagus and cook for 3–5 minutes until bright green and just tender.
Reduce the heat to medium-low. Pour in the chicken broth and add the cream cheese, Italian seasoning, onion powder, and remaining black pepper. Stir until the cream cheese melts into a smooth sauce.
Stir in the Parmesan until melted. If the sauce is too thick, add reserved pasta water or extra broth a tablespoon at a time.
Return the chicken and cooked penne to the skillet. Toss gently for 1–2 minutes until everything is coated in sauce.
Remove the skillet from the heat. Let it stand for about 30 seconds, then stir in the Greek yogurt. Add lemon juice if desired and adjust the seasoning.
Divide into six equal portions and garnish with parsley if using. Serve warm.