Climate change (CC) is one of the most challenging issues ever faced, as it affects every system worldwide at any scale. Urban areas are not an exception. Extreme weather-related events have seriously affected urban areas in recent years, and they have a significant impact on the welfare of people. According to UN projections, by 2050 more than 68% of the world’s population could be concentrated in urban areas. Additionally, daily life in urban areas is highly dependent on certain critical services and products provided by critical infrastructures (CIs). Therefore, it is especially relevant to understand how CC affects urban CIs in order to develop mechanisms to improve their capacity to handle crises derived from CC. In this context, resilience-based strategies provide a holistic approach, considering both predictable and unpredictable threats. This paper proposes a guide for assessing and enhancing the resilience level of cities against CC, considering urban CIs as key agents in improving the city’s capacity to face and recover from CC-related crises. The guide was developed through a co-creation process in which two cities in the Basque Country (Spain) worked together with CI providers and other relevant stakeholders in the resilience-building process. The resulting guide is to be used by city stakeholders at a strategic level, providing them with: (1) a qualitative assessment of the city’s current resilience level in the CC context; (2) better knowledge about urban CI sectors, their interdependency relationships and the chain of impacts due to cascading effects in the short, medium and in the long term and; (3) a set of policies that enhance city resilience.