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The tendency of modern designs towards optimal structures often leads to the lightest and best performing choice among a large set of design alternatives. In a similar scenario, the introduction of automated tools to further guide designers in achieving efficient solutions has been a recurrent topic for mechanical and structural engineers, over the past decades. Nowadays, topology optimization is considered a powerful preliminary design tool to determine the optimal material distribution in a design domain, i.e. the most effective configuration that satisfies a given set of prescribed constraints while reducing the consumption of structural material. Among different applications in the field of Civil Engineering, this work focuses on the definition of optimal layouts of lateral resisting systems for multi-storey steel building frameworks subject to lateral loads using topology optimization techniques. The objective of the research is to illustrate the benefits deriving from the introduction of automated routines within the preliminary design stage and establish reliable guidelines for performing accurate and objective optimization procedures. Since the optimal material distribution follows the load flow within the structure, optimal topologies are especially sensitive to the alteration of support and loading conditions: different loading scenarios naturally lead to distinct optimal layouts. In order to avoid the loss of objectivity and preserve the optimality of the results, the effects that preliminary modelling and loading assumptions produce on final layouts are investigated. Numerical applications to high-rise building models are presented and discussed.