Climate change poses significant challenges to perennial agricultural crops, including mulberry cultivation, which is essential for the silk industry and other uses. To address these challenges, it is crucial to improve the resilience of mulberry varieties to be able to adapt and stay productive. The development of climate-resilient varieties with improved tolerance to temperature extremes, drought, and salinity is one of the key focus areas of current mulberry research. Advances in plant biotechnology, such as genetic modification and molecular breeding, are pivotal in creating varieties with enhanced resilience to environmental stress and improved defense against pests and pathogens. In this direction, genetic improvement through creating transgenics and somatic hybrids has been tried to develop improved mulberry varieties. In addition, emerging omics platforms like advanced genomic sequencing technologies and transcriptomics have also been explored to understand the genetic architecture of mulberry and the discovery of resistance/tolerance genes that help mitigate abiotic and biotic stress. Research on precise modification in the genome using advanced genome editing tools has lots of scope for mulberry improvement. Also, advanced crop phenotyping techniques, viz., high-precision chlorophyll a fluorescence, infrared gas analysis, and plant hydraulics assessment methods, will be critical in identifying new functional targets for stress resilience and better yield under changing agroclimatic conditions. Further, functional trait phenotyping will help in early stress detection, large multilocational screening of mulberry germplasms, and characterization and identification of desirable genotypes. This book chapter explores current innovations in omics and biotechnological strategies and the prospects of functional trait phenotyping in mulberry improvement under climate change conditions.