This article successfully reviews practical considerations to manufacture nano-crystalline suspensions by top-down processes. The factors like formulation Composition, selection of milling steps and application of engineering principles are key aspects. In order to make a successful nano-crystalline suspension as a drug delivery system, the formulation and process engineering, have to be addressed based on physico-chemical principles, engineering methodologies and compliance to pharmaceutical regulation. Theoretical considerations of industrially employed milling technics like SBM and HPH are reviewed. The key fact on mathematical modelling and prediction tools (simulation scaling-down and scaling-up) are highlighted in detail. Formulation scientists and engineers needs to evaluate these factors and adjust according to API physicochemical properties and needs to be optimized case to case basis.