Reports by the Organisation for Economic Co-operation and Development (OECD) indicate that the average university dropout rate is 21%, rising to over 20% in countries such as Slovenia, Sweden, Colombia, Brazil, Spain and Chile. These high dropout rates mean that young people who decide not to continue with their academic training enter the labour market without adequate professional qualifications. Employers are increasingly requiring higher qualifications, and so having a university education is becoming essential for young people in order to access jobs that allow them a good quality of life, and therefore improve the quality of life of our societies. This, and other reasons—as we shall see throughout this chapter—indicate that studying the risk and protective factors of university dropout is a sine qua non condition for improving the quality of the educational system. The scientific literature addresses multiple variables related to studying the risk and protective factors of university dropout. These include the presence or absence of motivation, satisfaction with studies, and self-efficacy, as well as problems resulting from low self-esteem, academic stress, and assessment anxiety, etc. These factors have a negative impact on individual university students’ emotional, personal, social and academic well-being in their early youth (18–24 years of age, according to the World Health Organization). This chapter will address the problem of university dropout and the risk and protective factors associated with it, considering personal, social, academic and institutional variables related to the student. In addition, the chapter will review the measures that the scientific literature has proposed to improve students’ academic, social and personal well-being, emphasising the need to study the factors that are expected to help achieve comprehensive transformation of tertiary education.