The Covid-19 pandemic is more than a health crisis. It has worse outcomes among individuals with co-morbidities, has exposed fault lines in our societies, and amplified existing inequalities. This article draws on emerging evidence from low- and middle-income contexts to highlight how Covid-19 becomes syndemic when it interacts with local vulnerabilities. A syndemic approach provides a frame for understanding how Covid-19 is amplified when clustered with other diseases and how this clustering is facilitated by contextual and social factors that create adverse conditions. Public health responses to Covid-19 have also exacerbated these adverse conditions as many face social and economic crises as a result of some policies. These multiple challenges generate major implications for both the public health response and for broader development action: first, one size does not fit all and we must attend to local vulnerabilities; second, short-term public health response and longer-term development approaches must be integrated for improved intersectoral coordination and synergy. A synergised public health and development response will allow us to better prepare for the next pandemic.