Spread the broccolini, squash, and red onion on a baking sheet. Drizzle with 2 tablespoons of olive oil and season with salt and pepper. Toss to coat.
Roast the vegetables for 20 minutes, until the broccolini is beginning to crisp and the squash and onions are tender. Remove from the oven and set aside.
While the vegetables are roasting, make the spinach pesto: In a food processor, combine the spinach, walnuts, lemon zest, garlic, lemon juice, and red pepper flakes. With the processor running, slowly stream in the remaining ½ cup of olive oil until the pesto reaches a smooth, thick, and spreadable consistency.
Cook the orzo according to package instructions.
Add ¾ cup of the pesto to the warm orzo and toss to coat. Mix in the roasted vegetables and more pesto to taste.