Inoculating legume plants with indigenous rhizobial strains provides a foundation for evaluating their host compatibility and ability to adapt to different environmental conditions. Evaluating the ability of rhizobial strains to nodulate different legume species helps determine their suitability for application as biological inoculants. Cross-infectious, host range, and nitrogen fixation are the main aspects of plant-microbe symbiosis in legume-rhizobia interactions. Cross-infectivity is described as the ability of a microbial strain that is associated with multiple host plants, while host range refers to the spectrum of compatible plant species. Effectiveness of this process depends on the compatibility between host and strain, effectiveness of the formation of nodule, and physical environmental conditions such as soil nutrient status and climate. Expanding host range through cross-infective strains has significant implications for sustainable agriculture, such as improving crop yields in nitrogen-limited soils and reducing fertilizers. Therefore, this review merges the recent knowledge on the fundamental cross-infectivity and host range, and their direct impact on nitrogen fixation efficiency. It further explores advances in molecular biology and genomics that aim to manipulate these interactions for enhanced agricultural productivity. Understanding how host compatibility influences the effectiveness of rhizobial symbiosis is important for understanding the interaction between host specificity and symbiotic performance which is essential for development of effective bio-inoculants and promoting ecological sustainability in the agricultural system.