Lowering environmental impacts has lately been a critical objective of structural optimisation due to the significant amount of greenhouse gas (GHG) emissions in the civil engineering sector. This work introduces a Life Cycle Assessment (LCA) based multi-objective optimisation framework for the optimal design of mixed steel-timber structures by varying the building design’s size, shape, and topology. The study’s novelty stems from the integration of an environmental objective function in the early design process, based on LCA methodology and standard environmental indicators, and the definition of a structural target function where a penalty-based approach is implemented for reducing structural complexity in situ. The structural cost and the Global Warming Potential (GWP) are the objective functions of the optimisation problem. The analysis outcomes reveal that minimising the number of connections as well as moving towards timber-steel solutions represents the key aspect to achieve a sustainable and effective design of spatial truss structures.