Multi-module Cyber-Physical Systems (CPSs), such as satellite clusters, swarms of Unmanned Aerial Vehicles (UAV), and fleets of Unmanned Underwater Vehicles (UUV) are examples of managed distributed real-time systems where mission-critical applications, such as sensor fusion or coordinated flight control, are hosted. These systems are dynamic and reconfigurable, and provide a “CPS cluster-as-a-service” for mission-specific scientific applications that can benefit from the elasticity of the cluster membership and heterogeneity of the cluster members. The distributed and remote nature of these systems often necessitates the use of Deployment and Configuration (D&C) services to manage the lifecycle of software applications. Fluctuating resources, volatile cluster membership and changing environmental conditions require resilient D&C services. However, the dynamic nature of the system often precludes human intervention during the D&C activities, which motivates the need for a self-adaptive D&C infrastructure that supports autonomous resilience. Such an infrastructure must have the ability to adapt existing applications on-the-fly in order to provide application resilience and must itself be able to adapt to account for changes in the system as well as tolerate failures. This paper makes two contributions towards addressing these needed. First, we identify the key challenges in achieving such a self-adaptive D&C infrastructure. Second, we present our ideas on resolving these challenges and realizing a self-adaptive D&C infrastructure.