Agricultural production is under threat due to climate change in food insecure regions, especially in Asian countries. Various climate-driven extremes, i.e., drought, heat waves, erratic and intense rainfall patterns, storms, floods, and emerging insect pests have adversely affected the livelihood of the farmers. Future climatic predictions showed a significant increase in temperature, and erratic rainfall with higher intensity while variability exists in climatic patterns for climate extremes prediction. For mid-century (2040-2069), it is projected that there will be a rise of 2.8°C in maximum temperature and a 2.2°C in minimum temperature in Pakistan. To respond to the adverse effects of climate change scenarios, there is a need to optimize the climate-smart and resilient agricultural practices and technology for sustainable productivity. Therefore, a case study was carried out to quantify climate change effects on rice and wheat crops and to develop adaptation strategies for the rice-wheat cropping system during the mid-century (2040-2069) as these two crops have significant contributions to food production. For the quantification of adverse impacts of climate change in farmer fields, a multidisciplinary approach consisted of five climate models (GCMs), two crop models (DSSAT and APSIM) and an economic model [Trade-off Analysis, Minimum Data Model Approach (TOAMD)] was used in this case study. DSSAT predicted that there would be a yield reduction of 15.2% in rice and 14.1% in wheat and APSIM showed that there would be a yield reduction of 17.2% in rice and 12% in wheat. Adaptation technology, by modification in crop management like sowing time and density, nitrogen, and irrigation application have the potential to enhance the overall productivity and profitability of the rice-wheat cropping system under climate change scenarios. Moreover, this paper reviews current literature regarding adverse climate change impacts on agricultural productivity, associated main issues, challenges, and opportunities for sustainable productivity of agriculture to ensure food security in Asia. Flowing opportunities such as altering sowing time and planting density of crops, crop rotation with legumes, agroforestry, mixed livestock systems, climate resilient plants, livestock and fish breeds, farming of monogastric livestock, early warning systems and decision support systems, carbon sequestration, climate, water, energy, and soil smart technologies, and promotion of biodiversity have the potential to reduce the negative effects of climate change.