This chapter examines the emerging role of plant growth-promoting yeasts (PGPY), particularly Rhodotorula mucilaginosa, in sustainable agriculture through multifaceted plant–microbe interactions. As versatile ecosystem components, PGPY function not only as soil biofertilizers and biopesticides but also as indicators of holobiont health. R. mucilaginosa demonstrates remarkable physiological plasticity, conferring host plants with enhanced stress tolerance through nitrogen fixation, phosphate solubilization, phytohormone production, and pathogen suppression, while exhibiting bioremediation capabilities for pesticides and microplastics. The yeast’s efficacy has been validated through controlled studies, though field-scale validation remains necessary. A recent and significant finding involves R. mucilaginosa’s endosymbiotic nitrogen-fixing bacteria, suggesting it operates as a microecosystem that may contribute significantly to its plant-beneficial traits. Current research gaps include understanding the microholobiont’s full functional spectrum and potential for synthetic engineering. While PGPY-based technologies promise to reduce agrochemical dependence, key challenges persist in formulation optimization, regulatory harmonization, biosafety assurance, and shelf-life extension. The chapter synthesizes evidence from molecular mechanisms to field applications, proposing that optimized yeast consortia could form next-generation bioinoculants. However, successful implementation requires addressing interdisciplinary hurdles spanning microbiology, formulation science, and policy frameworks to realize the full potential of yeast-based solutions in sustainable crop production.