This study explores the prevalence, distribution, and codon usage bias of nematode species, primarily Heterodera glycines and Heterodera avenae, within saffron corms. Nematode analysis identified H. glycines and H. avenae as the predominant species. Geographical locations exhibited distinct cyst infestation levels, with H. avenae showing higher prevalence. The study reveals the preference of these nematodes for saffron corms, raising concerns for saffron production and suggesting the implementation of monitoring and management strategies. Additionally, the study analyzes the codon usage bias (CUB) of saffron and its associated nematode pathogens. Codon usage bias analysis revealed an AT bias in Crocus sativus and its pathogens. Codon Adaptation Index (CAI) values suggested pathogen adaptation to the host. Correlation analysis highlighted the interplay of nucleotide composition, mutational pressure, and natural selection in codon usage patterns. Amino acid frequency and codon context analyses provided insights into evolution and physiological functions. Furthermore, the study observed a mutual codon preference between the host and pathogens for certain amino acids, highlighting specific interactions at the molecular level. This study provides valuable information for understanding the molecular biology of plant-nematode interactions, and its findings can be useful for developing effective management strategies against these pests in saffron production and other crops such as crop rotation, use of resistant cultivars, and application of nematode-suppressive amendments.