A functional and reliable Health Information System (HIS) is vital for data-based decision-making in public health. Here we describe the assessment of data processes and general HIS principles by adapting a global approach to three cities. The assessments supported the data strategy of the CARDIO4cities initiative in each city aiming to improve urban population health by increasing the use of cardiovascular disease (CVD) data to inform decision-making. We aimed to explore data collection processes and entities, data availability and quality as well as data ownership and sharing regarding a set of identified key performance indicators (KPIs). KPIs were based on a global theory of change (ToC) and a global evaluation and indicator framework and were tailored to each location. By first assessing existing sources and processes regarding data, recommendations for changes and improvements are sure to build on current circumstances. To map the data, existing data collection, analysis and storage processes were investigated. A flow chart was created to visualize the data pathways and challenges for each system and findings were compared across cities to document differences and similarities. Data quality and interoperability of various separate systems were the most prominent challenges for all HISs. The observed dvata quality issues originated from incorrect, missing and incomplete data and were connected to the misunderstanding of indicators, incomplete data input forms or the lack of a systematic data routine in the workflow. Harmonization of the HISs to ensure interoperability can facilitate data collection and analysis of health data and can provide a solid basis for health management decision-making. Based on the presented HIS cases, we recommend to examine, map and verify current processes when conducting a HIS assessment, to visualize findings and to gauge the interest of government entities to ensure political support.