In this talk, I will discuss the design of application-aware self-optimizing systems through automated resource management that helps meet the varied goals of the provider and applications in large-scale networked environments. The key steps in closed-loop resource management include learning of application resource needs, efficient scheduling of resources, and adaptation to variations in real time. I will describe how I apply this high-level approach in two distinct environments using (a) Morpheus in enterprise clusters, and (b) Patronus in cellular provider networks with geo-distributed micro data centers. I will also touch upon my related work in application-specific context at the intersection of network scheduling and deep learning. I will conclude with my vision for self-optimizing systems including fully automated clouds and an elastic geo-distributed platform for thousands of micro data centers.