Human activities are driving unprecedented increases in atmospheric CO2 concentrations, resulting in global warming, with a higher frequency of marine heat waves (MHWs), and ocean acidification (OA) that represent a critical threat to coastal seagrass habitats. To assess the potential impacts and to deepen the knowledge on the long-term adaptive responses to these stressors, Posidonia oceanica meadows have been investigated in natural CO2 vent systems of Ischia (Italy) and Panarea (Aeolian Archipelago, Italy) islands, where continuous volcanic gas emissions create chronically acidified conditions, with CO2 concentrations comparable to those projected by the IPCC report of 2023 for 2030, as well as to examine the combined effects of OA and MHW on P. oceanica and its associated fauna. In this context, a meta-analysis was conducted to quantify the relative contributions of OA, MHW and hypersalinity (a climate driver strictly related with higher temperature, affecting shallowest ecosystems and already affecting some habitats due to brine discharges) to the impact on the responses of P. oceanica studied in mesocosms with long-term exposures and natural laboratories. This study aims to summarise the physiological and cellular responses (excluding genetic analysis) to the aforementioned stressors, to underline the interactions between them, and their impacts on P. oceanica, and to focus attention where future studies should be directed. The results of the meta-analysis highlight a consistent negative pattern in P. oceanica growth due to the analysed stressors, a strong negative impact on calcifying associated fauna due to OA, and an important negative effect on photosynthesis caused by hypersalinity. At the same time, there is clear evidence of a substantial gap in the study of response variables associated with the impact of warming and MHW. These findings emphasize the possible future consequences and highlight the importance of deepening knowledge of multiple-stressor exposure effects and developing conservation programs.