With an electricity system defined by high shares of hydropower, large capacity for interconnection with its neighbours and low carbon intensity, Switzerland is well positioned to attain its objective of net zero carbon emissions by 2050. However, the exact pathway remains the subject of discussion. First, what should the shares of nuclear energy and variable renewable energies such as solar PV and wind be in the energy mix? Second, what degree of electricity trade should Switzerland have with its European neighbours? New system modelling of different energy policy choices with the Nuclear Energy Agency’s POSY model shows that all considered scenarios are technically feasible. However, relying on variable renewables alone or decoupling Switzerland from neighbouring countries could increase total system costs by up to 250%. Instead, continuing to operate Switzerland’s newest nuclear power plants alongside existing hydropower resources, while maintaining interconnection capacity at current levels, emerges as the most cost-effective option to achieve net zero emissions in 2050. Ample data and technical documentation of a least-cost mixed integer (MILP) modelling with hourly resolution are also provided in order to allow replication, extension and discussion of this study’s findings.