Among the innovative technologies being elaborated for sustainable agriculture, one of the most rapidly developing fields relies on the positive effects of non-thermal plasma (NTP) treatment on the agronomic performance of plants. A large number of recent publications have indicated that NTP effects are far more persistent and complex than it was supposed before. Knowledge of the molecular basis and the resulting outcomes of seed treatment with NTP is rapidly accumulating and requires to be analyzed and presented in a systematic way. This review focuses on the biochemical and physiological processes in seeds and plants affected by seed treatment with NTP and the resulting impact on plant metabolism, growth, adaptability and productivity. Wide-scale changes evolving at the epigenomic, transcriptomic, proteomic and metabolic levels are triggered by seed irradiation with NTP and contribute to changes in germination, early seedling growth, phytohormone amounts, metabolic and defense enzyme activity, secondary metabolism, photosynthesis, adaptability to biotic and abiotic stress, microbiome composition, and increased plant fitness, productivity and growth on a longer time scale. This review highlights the importance of these novel findings, as well as unresolved issues that remain to be investigated.