AbstractIntegrating physical knowledge and machine learning is a critical aspect of developing industrially focused digital twins for monitoring, optimisation, and design of microalgal and cyanobacterial photo‐production processes. However, identifying the correct model structure to quantify the complex biological mechanism poses a severe challenge for the construction of kinetic models, while the lack of data due to the time‐consuming experiments greatly impedes applications of most data‐driven models. This study proposes the use of an innovative hybrid modelling approach that consists of a simple kinetic model to govern the overall process dynamic trajectory and a data‐driven model to estimate mismatch between the kinetic equations and the real process. An advanced automatic model structure identification strategy is adopted to simultaneously identify the most physically probable kinetic model structure and minimum number of data‐driven model parameters that can accurately represent multiple data sets over a broad spectrum of process operating conditions. Through this hybrid modelling and automatic structure identification framework, a highly accurate mathematical model was constructed to simulate and optimise an algal lutein production process. Performance of this hybrid model for long‐term predictive modelling, optimisation, and online self‐calibration is demonstrated and thoroughly discussed, indicating its significant potential for future industrial application.