The increasing use of model-driven software development has renewed emphasis on using domain-specific models during application development. More specifically, there has been emphasis on using domain-specific modeling languages (DSMLs) to capture user-specified requirements when creating applications. The current approach to realizing these applications is to translate DSML models into source code using several model-to-model and model-to-code transformations. This approach is still dependent on the underlying source code representation and only raises the level of abstraction during development. Experience has shown that developers will many times be required to manually modify the generated source code, which can be error-prone and time consuming. An alternative to the aforementioned approach involves using an interpreted domain-specific modeling language (i-DSML) whose models can be directly executed using a Domain Specific Virtual Machine (DSVM). Direct execution of i-DSML models require a semantically rich platform that reduces the gap between the application models and the underlying services required to realize the application. One layer in this platform is the domain-specific middleware that is responsible for the management and delivery of services in the specific domain. In this dissertation, we investigated the problem of designing the domain-specific middleware of the DSVM to facilitate the bifurcation of the semantics of the domain and the model of execution (MoE) while supporting runtime adaptation and validation. We approached our investigation by seeking solutions to the following sub-problems: (1) How can the domain-specific knowledge (DSK) semantics be separated from the MoE for a given domain? (2) How do we define a generic model of execution (GMoE) of the middleware so that it is adaptable and realizes DSK operations to support delivery of services? (3) How do we validate the realization of DSK operations at runtime? Our research into the domain-specific middleware was done using an i-DSML for the user-centric communication domain, Communication Modeling Language (CML), and for microgrid energy management domain, Microgrid Modeling Language (MGridML). We have successfully developed a methodology to separate the DSK and GMoE of the middleware of a DSVM that supports specialization for a given domain, and is able to perform adaptation and validation at runtime.