Soilless systems, such as hydroponics and aquaponics, are gaining popularity as a sustainable alternative to traditional soil-based agriculture, aiming at maximizing plant productivity while minimizing resource use. Nonetheless, the absence of a soil matrix poses challenges that require precise management of nutrients, effective control of salinity stress, and proactive strategies to master disease management. Plant growth-promoting microorganisms (PGPM) have emerged as a promising solution to overcome these issues. Research demonstrated that Bacillus, Pseudomonas, and Azospirillum are the most extensively studied genera for their effectiveness as growth promoters, inducing changes in root architecture morphology. Furthermore, PGPM inoculation, either alone or in synergy, can reverse the effects of nutrient deficiency and salt stress. The genera Pseudomonas and Trichoderma were recognized for their solid antagonistic traits, which make them highly effective biocontrol agents in hydroponic systems. The latest findings indicate their ability to significantly reduce disease severity index (DSI) through mycoparasitism, antibiosis, and induced systemic resistance. In aquaponic systems, the inoculation with Bacillus subtilis and Azospirillum brasilense demonstrated increased dissolved oxygen, improving water quality parameters and benefiting plant and fish growth and metabolism. This review also establishes the interaction variability between PGPM and growing media, implying the specificity for determining inoculation strategies to maximize the productivity of soilless cultivation systems. These findings suggest that using PGPM in soil-free settings could significantly contribute to sustainable crop production, addressing the challenges of nutrient management, disease control, and salinity issues.