Systems and methods are described to enable adaptive handling of domain resolution requests originating from a virtual private cloud (VPC) networking environment. An administrator of the VPC can provide a set of rules specific to the VPC that designates how requests for a domain name should be handled. The rules may specify, for example, that a request for a given domain name should be routed to a particular domain name server, which may include a private domain name server, should be dropped, or should be routed according to a default behavior (e.g., a public domain name system). Resolution requests originating in the VPC can be associated with a VPC identifier. When an adaptive resolution system receives the request, it can retrieve rules associated with the VPC identifier, and apply the rules to determine further routing for the request.