Cyber-Physical Systems (CPS) produce behavior through execution on substrates coupling computation with physical processes. However, usual engineering approaches do not treat execution semantics as first-class engineering entities. Formal verification reasons about model behaviors under fixed semantic assumptions that are not revisable and do not account for physical execution constraints. Simulation-based validation explores scenarios under execution semantics that are implicitly determined by the simulation engine. In both cases, physical constraints of the execution substrate are addressed as implementation details rather than as semantic boundary conditions. In this article, it is hypothesized that making execution semantics explicit as first-class engineering entities is necessary and sufficient to bridge the gap between verified model behaviors and validated executed behaviors in CPS. To test this hypothesis, Modeling and Simulation Based Engineering (MSBE) is proposed: a methodology grounded in the Theory of Modeling and Simulation. MSBE formalizes execution conditions as four components: execution semantics, activity (behaviorally meaningful changes), admissibility constraints (physical bounds), and specified properties (behavioral guarantees). MSBE organizes engineering around an iterative cycle alternating formal execution, experimental execution, verification, and activity-mediated validation. Executability is defined as stabilization of execution conditions and the induced admissible model space. The cycle is applied to four CPS classes (human-centric, biophysical, technological, and digital twins). These applications show that the framework generalizes beyond CPS to any system whose behavior depends on explicitly defined execution conditions. Modeling and Simulation-Based Engineering