Key message: The increase in climate variability is likely to generate an increased occurrence of both frost-induced and drought-induced damages on perennial plants. We examined how these stress factors can potentially interact and would subsequently affect the vulnerability to each other. Furthermore, we discussed how this vulnerability could be modulated by shifts in the annual phenological cycle. Context: The edges of plant distribution are strongly affected by abiotic constraints: heat waves and drought at low latitude and elevation, cold and frost at high latitude and elevation. The increase in climate variability will enhance the probability of extreme events and thus the potential interaction of stress factors. The initial exposure to a first constraint may affect the vulnerability to a subsequent one. Aims: Although three integrative physiological processes, namely water balance, carbon metabolism and the timing of phenological stages, have largely been studied in the response of trees to a single constraint, their interaction has rarely been investigated. How would the interaction of frost and drought constraints modulate the vulnerability to a subsequent constraint and how vulnerability to a given constraint and phenology interact? Conclusion: We suggest that the interaction between frost and drought constraints should in the short-term influence water balance and, in the longer term, carbon metabolism, both consequently affecting further vulnerability. However, this vulnerability can be modulated by shifts in the annual phenological cycle. Significant gaps of knowledge are reported in a mechanistic framework. This framework can help to improve the current process-based models integrating the life history of the individual plant.