This study is based on the perspective of “Three Comprehensive Education” to explore thepsychological problems of post-00s college students. Taking a certain university as an example, a total of3812 students were selected as the research subjects. It was found that in terms of emotional risk factors,male students perceived higher levels of depression, anxiety, and loneliness than female students; Thelevel of depression, anxiety, and loneliness perceived by senior students is higher than that of othergrades. At the level of network risk factors, male students have higher levels of gaming addiction, onlinebullying, and online victimization than female students, while female students have higher levels of onlineobservation than male students; The level of game addiction among third year students is higher than thatof other grades, while the level of online bullying and victimization among fourth year students is higherthan that of other grades. Among them, fourth and third year students have the highest level of onlineobservation. Based on research data analysis, this study explores personalized intervention strategiesfor the psychological problems of post-2000s college students, namely: constructing a new model of“party building+psychological prevention” from the perspective of “three comprehensive education”, andimproving the online mental health education curriculum system for their low-risk emotional risk groupand low-risk network risk group groups mainly based on the MOOC platform; The flipped classroomteaching model is mainly used to expand and extend the mental health education curriculum for the highriskemotional group and the high-risk network group groups; provide characteristic group counselingand individual psychological counseling for their high-risk emotional risk group and high-risk networkrisk group groups, in order to provide certain reference value for the mental health education work ofcollege students.