The impact of psychological factors is increasingly taken into consideration in cancer patient care. In this review, we focus on the explicative models and the factors involved in psychosocial adaptation to cancer. Concerning the former, we present the latest reviews on stress and coping paradigm as applied to psycho-oncology. Specifically, we discuss the psychological mechanisms that make it possible to manage emotional distress related with cancer and that determine the different degrees of adaptation to the disease. This explanation is illustrated with two examples. On the other hand, the role of several variables that influence adaptation to cancer, grouped as sociocultural, psychological and medical variables, is discussed. Sociocultural variables make it possible to identify which patients have an increased risk of developing psychological distress symptoms. The psychological variables, include the different coping strategies, psychiatric history, psychological distress and concerns and fears. The impact of sociocultural and psychological variables is illustrated with two case examples. The medical variables are associated with the disease stage, treatment and prognosis. Finally, we discuss in what way these models, concepts and factors allow for design interventions adapted to the specific needs of each patient.