An apparatus in one embodiment comprises a processing platform configured to implement multi-layer infrastructure comprising compute, storage and network resources at a relatively low level of the multi-layer infrastructure and an application layer at a relatively high level of the multi-layer infrastructure. The processing platform is further configured to determine operational policies for respective different ones of the layers of the multi-layer infrastructure other than the application layer, the operational policies defining operational rules and requirements relating to the corresponding layers, to determine an application policy for the application layer, the application policy defining application workload rules and requirements for an application to be executed in the multi-layer infrastructure, and to manage the multi-layer infrastructure in accordance with the operational policies and the application policy. The operational policies are defined independently of the application policy but mutually enforced with the application policy in conjunction with execution of the application in the multi-layer infrastructure.