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Abstract The COVID-19 pandemic created enormous public health and socioeconomic challenges. The health effects of vaccination and non-pharmaceutical interventions (NPIs) were often contrasted with significant social and economic costs. We describe a general framework aimed to derive adaptive cost-effective interventions, adequate for both recent and emerging pandemic threats. We also quantify the net health benefits and propose a reinforcement learning approach to optimise adaptive NPIs. The approach utilises an agent-based model simulating pandemic responses in Australia, and accounts for a heterogeneous population with variable levels of compliance fluctuating over time and across individuals. Our analysis shows that a significant net health benefit may be attained by adaptive NPIs formed by partial social distancing measures, coupled with moderate levels of the society’s willingness to pay for health gains (health losses averted). We demonstrate that a socially acceptable balance between health effects and incurred economic costs is achievable over a long term, despite possible early setbacks.