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Nowadays, the need for more contributions from renewable energy sources is rapidly growing. This is forced by many factors including the requirements to meet the targeted reductions of greenhouse gas emissions as well as improving the security of energy supply. According to the International Renewable Energy Agency (IRENA) report 2016, the total installed capacity of solar energy was at least 227 GWs worldwide by the end of 2015 with an annual addition of about 50 GWs in 2015, making solar power the world’s fastest growing energy source. The majority of these are grid-connected photo voltaic (PV) solar power plants, which are required be integrated efficiently into the power grids to meet the requirements of power quality standards at the minimum total investment cost. For this, multilevel voltage source inverters (VSI) have been applied extensively in recent years. In practice, there is a trade-off between the inverter’s number of levels and the required size of output filter, which is a key optimisation area. The aim of this research is to propose a generic model to optimise the design number of levels for the Cascaded H-Bridge Multilevel Inverter (CHB-MLI) and the size of output filter for medium voltage – high power applications. The model is based on key measures, including inverter power loss minimisation, efficient control for minimum total harmonic distortion (THD), minimisation of total system cost and proposing the optimum size of output filter. This research has made a contribution to knowledge in the optimisation of CHB-MLI for medium-voltage high-power applications, in particular, the trade-off optimisation of the inverter’s number of levels and the size of the output filter. The main contribution is the establishment and demonstration of a sound methodology and model based on multi-objective optimisation for the considered key measures of the trade-off model. Furthermore, this study has developed a generic precise model for conduction and switching loss calculation in multilevel inverters. Moreover, it applied Genetic Algorithm (GA) optimisation to provide a complete optimum solution for the problem of selective harmonic elimination (SHE) and suggests the optimum size of output passive power filter (PPF) for different levels CHB-MLIs. The proposed trade-off optimisation model presents an efficient tool for finding the optimum number of the inverter’s levels and the size of output filter, in which the integration system is at its lowest cost, based on optimisation dimensions and applied system constraints. The trade-off optimisation model is generic and can be applied to any multilevel inverter topologies and different power applications.