Isoelectronic cation substitution is a potential method to decrease the density of Cu‐Zn anti‐site defects in CZTSSe, thus improving the VOC and performance of CZTSSe solar cells. The proper doping concentration is determined traditionally by the trial and error approach, costing much time, and materials. How to shorten the time to find the proper doping concentration is a big challenge for the development of solar cells. Here, by utilizing the machine learning model, the authors carry out an adaptive design for predicting the optimal doping ratio of Mn2+ ions in CZTSSe solar cells for improved solar cell efficiency. With the help of machine learning prediction, the authors rapidly and efficiently find the optimal doping ratio of Mn2+ in CZTSSe solar cells to be 0.05, achieving a highest solar cell efficiency of 8.9% in experiment. Further experimental characterizations of Mn‐doped CZTSSe show that the defect in CZTSSe after Mn doping is changed from an anti‐site CuZn defect to VCu defect. Our findings suggest that machine learning is a very powerful and efficient approach to aid the development of solar cell materials for its application in the photovoltaic field.