Switzerland has one of the lowest carbon intensities among industrialised countries. However, its transition to net-zero carbon dioxide emissions is complicated by limited domestic mitigation options, which tend to increase costs, raise energy security concerns, and trigger socio-economic barriers in policy implementation. Research on these issues is relevant to the societal and political debates on energy transition worldwide. Here we apply a well-established techno-economic energy systems model and highlight the challenges of the Swiss energy transition under different technical, socio-economic, and geopolitical contexts. We suggest feasible technical solutions based on low-carbon technologies, efficiency, and flexibility. We find that import independency and net-zero emissions by 2050 require an additional cumulative discounted investment, compared to a business-as-usual scenario, of 300 billion CHF₂₀₁₉ in energy efficiency, negative emissions and renewable technologies. The average per capita costs of net-zero emissions are 320–1390 CHF₂₀₁₉/yr. from 2020 to 2050, depending on exploited domestic mitigation options, integration into international energy markets, and energy security ambition.