Bring a large pot of lightly salted water to a boil. Add penne and cook, stirring occasionally, until tender yet firm to the bite, about 11 minutes. Drain and set pasta aside.
Combine cashews, miso paste, garlic, and hot water in a high frequency blender (such as a Vitamix®). Turn on Vitamix® and quickly increase speed to 10. Blend until mixture is fully blended, 6 to 8 minutes. The mixture should steam when you remove the lid. Pour sauce over pasta and serve - sauce will thicken up as it cools.