Practicing mulberry cultivation and silkworm rearing with minimal environmental impact and promoting better ecological balance is essential to attain sustainability in sericulture. However, climate variability from the past decade has had a significant impact on attaining sustainability in sericulture. As climate variability increasingly affects the farming sector worldwide, sericulture—a delicate industry depending on specific environmental conditions for both mulberry cultivation and silkworm rearing is facing significant risks. This chapter explores the intricate relationship between climate change and mulberry cultivation, focusing on adaptation strategies, challenges, and mitigation efforts to attain sustainability. Climate change poses significant challenges in mulberry cultivation by altering temperature, CO2 concentration, humidity, and rainfall levels, which are critical for the growth and development of mulberry. Due to temperature fluctuations, altered precipitation patterns, and increased frequency of extreme weather events, many challenges need to be addressed, which include water stress, shift in pest population dynamics, and outbreak of plant diseases, which are responsible for significant reductions in crop yield. We delve into various adaptation strategies that can be employed under changing climatic conditions, such as the development of climate-resilient cultivation practices, sustainable soil and water management techniques, organic farming, biotic and abiotic stress tolerance, and mulberry varieties that can enhance resilience. By compiling current research and field observations, this chapter provides a comprehensive overview of these challenges, adaptive strategies, and innovative solutions to maintain the viability and productivity of mulberry cultivation in a changing climate for attaining sustainability.