The global population is predicted to expand to 9.1 billion by 2050. Countries around the Mediterranean Sea are predicted to achieve a combined population of 529 million by 2025. The current major challenge confronting sustainable agriculture in the Mediterranean region is climate change which has directly affected the extent and frequency of rain events, floods, and droughts, which in turn has influenced land and water productivity and farmers’ livelihoods. The present review highlights the major consequences of climate change for sustainable crop production in the Mediterranean region and evaluates different mitigation strategies for improving agricultural land productivity and water use efficiency along with their impact on farmers’ livelihoods.