The synthesis/design and operation of large scale industrial process/systems has as an integral part the selection of systems of measurement and actuation variables. The selection of systems of measurement and actuation variables has a significant effect on the shaping of the final system and thus it is crucial in defining the control quality properties (process controllability) and operability characteristics of the final design. This paper examines the fundamental system and Control Theory issues involved in the selection of systems of measurement and actuation variables and introduces four clusters of system and control problems. These ore the : (i) Model Orientation Problems, (ii) Model Projection Problems, (iii) Model Composition Problems and (iv) Model Expansion Problem. A structural approach for studying these problems is introduced and for a number of them, their link to standard Control theory Problems is established.