At the request of the Regional Health Agency (ARS) in the Provence-Alpes-Côte d'Azur (PACA) region, and with the support of Santé publique France in the PACA and Corsica regions, as well as UMR1252 SESSTIM (Aix-Marseille University, INSERM, IRD), the associations Corhesan and Sept have developed a health mediation project targeting vulnerable populations in Marseille (the "13 en santé" project). The main objective of this project is to promote cancer screening (cervical, breast, and colorectal) and to update vaccination schedules. It includes several evaluation components, including a cross-sectional survey to estimate the level of vaccine hesitancy, the rate of participation in cancer screenings, vaccination coverage for the DTP booster and against human papillomavirus (HPV), and levels of knowledge, attitudes, and barriers to cancer screening and vaccination. A baseline survey was conducted in September 2022 by the Corhesan and Sept associations among individuals aged 18 to 74 living in vulnerable neighborhoods in the center and north of the city of Marseille. The sample size was estimated based on the screening rate of the eligible population for each program, aiming for a total of 2,400 participants. Statistical associations between non-participation in screening and vaccination and sociodemographic factors were analyzed using unadjusted univariate and multivariate logistic regression models. In total, interviewers surveyed 2,647 people door-to-door using a standardized questionnaire. Regarding cancer screening, participation rates for breast, cervical, and colorectal cancer screening (51%, 68%, and 31%, respectively) are lower than the national rates in France. Being aware of screening and having received an invitation letter strongly encourage participation. The absence of symptoms is the main barrier cited for participation in cancer screening (18% to 50% depending on the cancer). Regarding vaccination, there is low awareness of the HPV vaccine (43% of women and 17% of men aged 18–35). HPV vaccination coverage among women aged 18–35 is 24% and is strongly associated with awareness of the vaccine. Vaccination coverage for the adult DTP booster (51%) is comparable to the national coverage rate. However, one-third of the population is unaware of this vaccination. Overall, 72% of respondents report being in favor of vaccination with moderate vaccine hesitancy (median=60, [95% CI 45–71]). However, 20% of the population in the northern neighborhoods and 10% in the central neighborhoods report high vaccine hesitancy. These results highlight the importance of improving knowledge among vulnerable populations in the northern and central neighborhoods of Marseille regarding cancer screening procedures and vaccination against HPV and the adult DTP booster. This could help increase participation rates in cancer screening as well as vaccination coverage. It is also essential to raise public awareness of the importance of getting screened for cancer even in the absence of symptoms and to reduce vaccine hesitancy among a portion of the population. Health mediation through outreach, collaboration, and follow-up can address the needs for support and targeted information tailored to the diverse population profiles in these neighborhoods.