Due to its profitability as well as low-water and -nutrient requirements, saffron (Crocus sativus L.) has been vastly promoted and recommended as an alternative plant in arid and semi-arid agricultural systems. Soil fertility guarantees sustainable nutrient availability for plants and biomass production. Accordingly, this study aimed to investigate the interaction effects between organic and chemical fertilizers and mycorrhizal inoculation on some soil characteristics, plant nutrient composition, and biomass production of saffron. To this purpose, we compare the experimental results of two growing seasons (2015–2016 and 2016–2017) obtained under semi-arid conditions. The experiment consisted of different nutrient management approaches: control (non-amended soil), compost (COM), compost + biochar (COM + B), and chemical fertilizers (CF), which were either inoculated or non-inoculated with arbuscular mycorrhizal (AM) fungus (Glomus mosseae). The results indicated that CF fertilization significantly increased the total biomass, nutrient uptake, and nutrient use efficiency of saffron when inoculated with AM. Findings also showed that applying merely organic amendments not only led to a significantly higher soil pH, available phosphorus (P), soil organic carbon (SOC), cation exchange capacity, and lower bulk density but also had positive effects on total biomass, nutrient uptake, and nutrient use efficiency in AM-inoculated plots. We also found that inoculation of organically-amended plots with AM increased the soil-available P by raising SOC decomposition during the growing season of 2015–2016, which was accompanied by higher P uptake and P use efficiency, especially over the season of 2016–2017. Further, lower nitrogen uptake (NU), lower nitrogen use efficiency (NUE), as well as lower soil N content were recorded in COM + B and non-amended soils. This decline can be attributed to higher C: N ratios, meaning that C: N ratio was negatively correlated with N acquisition parameters. However, AM-inoculation significantly increased N content and subsequently N acquisition in COM-amended soil. Based on the results of this study, it is safe to say that applying chemical fertilizers inoculated by AM can be considered as an approach to enhance nutrient acquisition and biomass production of saffron. Moreover, we managed to improve soil characteristics and saffron nutrient composition through integrated application of AM and compost, which can be another helpful approach to maintain soil fertility and enhance yield potential of saffron fields in semi-arid regions.