Background: Population ageing and the consequent growing up of multiple chronic diseases are increasing long-term care (LTC) demand worldwide. In Europe and beyond, regardless of the welfare regime, the bulk of care for older people is carried out by informal caregivers (ICGs), often adults and older adults. Nevertheless, recently, many studies shed light on young people playing the role of caregivers (named Adolescent Young Carers-AYCs) of frail older family members, often grandparents (GrPs). Intergenerational caregiving negative outcomes (e.g. high level of stress and poor physical health and mental well-being) can occur, especially in countries with under developed LTC systems. The COVID-19 outbreak represented a real “stress-test” for the European LTC systems, bringing to light their limits and weaknesses. The virus containment measures exacerbated the living and health conditions of ICGs and non-self-sufficient older adults by restricting the possibility of accessing many social and health services. The overall aim of this work is to deeper the characteristics of intergenerational caregiving both in ordinary circumstances and in Pandemic time, with the ambition of providing a new conceptual framework for its interpretation. Methods: Four studies were carried out between 2020 and 2022. Studies 1 and 2 report the results of a survey targeted to AYCs aged 15–17, carried out in the framework of the Me-We project “Psychosocial support for promoting mental health and well-being among young adolescent caregivers in Europe”, which received funding by the European Union’s Horizon 2020 research and innovation programe (H2020; 2018-2021) under grant agreement No. 754702. Study 1 compares a sub-sample of AYCs of GrPs to another sub-sample of AYCs of other care recipients (OCRs), e.g., parents, siblings, and friends. The analysis included a final sample of 817 AYCs. Linear or logistic regression models were built, and multivariate analyses were repeated. Study 2 considers two sub-samples of 87 AYCs living in Italy and 75 living in Slovenia. A multiple linear regression model was built for the quantitative data. Qualitative data were content analysed using an open coding process. Studies 3 and 4 report the results of an online survey reaching 2,468 European caregivers from 16 countries, carried out in Winter 2020/2021. Study 3 focused on two sub-samples of ICGs of older people with LTC needs living in Germany and Italy (149 and 173, respectively). A logistic regression analysis was performed by country to obtain an adjusted estimate of the risk of worsening caregivers’ health. Study 4 focused on 1,390 ICGs and compared the effects of the Pandemic on two sub-samples of 848 adult caregivers (ACGs) and 542 older caregivers (OCGs). The differences between the two groups were estimated using logistic regression and adjusted for all potential confounders. All analyses were repeated after propensity scores (PS). Results: Study 1: AYCs of GrPs experienced more positive caregiving outcomes than AYCs of OCRs across the six countries included in the analysis. Being female or non-binary, and having a migration background, were associated with more negative outcomes. Study 2: 80% of respondents were females and one out of three AYCs reported health problems due to their caring responsibilities. Italian respondents faced communicative and practical problems, while Slovenians experienced mainly emotional discomfort. Study 3: the risk of worsening caregivers’ health increased by more than 40% for German caregivers compared to Italian ones, despite the former receiving more formal services than the second ones. Furthermore, the overall health risks and protecting factors differed by country. Study 4: ACGs experienced more worsening physical conditions, took care of older relatives with more severe health conditions and increased the hours of care more than OCGs. Regardless of age, females were more exposed to health risk and poor quality of life than males. Also new caregivers were mainly females and their physical health and quality of life were put at risk by caregiving. Discussion: The four studies confirmed the overwhelming presence of women in formal intergenerational caregiving, underlining they are at greater health risk than males at any age and at any time. The COVID-19 outbreak has only exacerbated gender inequalities in the distribution of care tasks. The quick interruption of care services and the overall stressful situation given by the global health crisis did not allow ICGs to make a proper and timely appraisal of their situation, causing an evident deterioration in their overall health conditions. Conclusions: Results call for reforms of LTC systems across Europe boosting in-home care and providing more practical and psychological support targeted to ICGs of all ages. Moreover, further research on gender inequalities in intergenerational caregiving is recommended. The Intergenerational Caregiving Appraisal and Stress Model (ICASM), an original theoretical framework, is proposed as a possible lens to interpret the experience of today intergenerational caregiving, characterized by older care recipients with chronic diseases and multimorbidities and by women with multiple social roles.