The main purpose of this chapter is to present and to discuss the implementation and the main methodological characteristics, notably in terms of design and research protocol, sampling and data collection procedure via a mixed-mode approach, of our 7-year longitudinal study on professional trajectories. More specifically, adopting several psychological perspectives, this study addresses professional transitions and career pathways and personal experiences – particularly in terms of well-being – of employed and unemployed middle-aged adults (25–55 years) living in Switzerland. Furthermore, based on the first wave of data (N = 2469), we introduce some results concerning, amongst others, the predictors of the choice of the mode to complete the questionnaire and of the intention to participate in the next wave, and possible differences on vulnerability indicators with reference to personal characteristics, resources and professional situation. Finally, considering the procedure implemented and the results emerging from this first wave, we discuss several implications and challenges for the next waves.