In the face of climate adversities, the challenges faced by agricultural practices, depleting natural resources, rising hunger, and malnutrition necessitate harnessing bio-based resources, guided by the Sustainable Development Goals (SDGs) and transformative actions. For the development of sustainable food systems and climate-resilient crops, seed biopriming with beneficial microbes is gaining increased recognition, attributed to their favorable impact on plant growth, nutrient acquisition, and defense against pathogens. 'Seed primeomics' is a key concept in seed priming, and emphasizes the retention of stress memories, transgenerational microbial interactions, and plant stress resilience, as demonstrated by Trichoderma harzianum modulation of epigenetics in Lycopersicum esculentum roots. With an expanding scope, next-generation breakthroughs in nano-enabled seed biopriming can potentially address concerns associated with the performance and efficacy of the bio-inoculants in field conditions, as evident by ZnO nanopriming in fragrant rice, resulting in micro-nutrient fortified crops. Furthermore, encapsulation of microbial inoculants with nano-based polymers promotes plant development, while the nanoencapsulation procedure safeguards microbial strains and promotes shelf-life and controlled release, addressing key limitations with commercial applications. While the prospects of seed biopriming are immense and define novel avenues in sustainable agricultural practices, further research is essential to bridge the knowledge gaps. Herein, the article provides insights into how endophyte-mediated seed biopriming, as a potent and cost-effective green technology, is defining new avenues in ecosystem restoration, plant stress tolerance and adaptation, and the creation of climate-resilient crops capable of tolerating fluctuating climates, marking a new era in climate-smart agriculture.