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Organic amendment and green manuring are two agricultural practices highly recommended to improve sustainability in agriculture since they show numerous beneficial effects on both soils and crops. The main aim of the present study was to evaluate the effect of both, specifically organic fraction municipal solid waste (OFMSW) compost and horse bean (Vicia faba L., cv minor) green manure, combined separately or together with a mineral fertilization using synthetic products and in comparison with a mineral fertilization alone (control), on a top-quality tobacco crop (dark fire-cured Kentucky) grown in the cultivation district of Central Italy (High Tiber Valley, Tuscany region) in 2020 and 2021. The following parameters were measured: (i) leaf emergence rate (LER, leaves day−1); (ii) crop growth rate (CGR, kg dry biomass ha−1 day−1); (iii) root weight density (RWD, mg cm−3); (iv) yield of cured product (CLY, Mg ha−1). Analytical determinations were carried out on soil, sampled at the 0–0.3 m depth (organic matter, %; total N, %; NO3-N, mg kg−1; C/N; P and K, mg kg−1), and on plant biomass (total N, %; NO3-N, kg ha−1). Soil water retention measures were also made. Water productivity (WP, kg cured product m−3 gross crop evapotranspiration, ETc gross), irrigation water use efficiency (IWUE, kg cured product m−3 seasonal irrigation volume) and N agronomic efficiency (NAE, kg cured product kg−1 mineral N applied by synthetic fertilizers) were calculated. Both the applications of OFMSW compost and horse bean green manure increased soil content of organic matter and main nutrients (N, P and K), as well as C/N, when compared with control conditions. There was an increase in soil water content in C conditions over the entire soil matric potential interval (0.04 to 1.2 MPa) with a maximum value at 1.2 MPa in both years. Both practices appeared promising for tobacco cultivation and could help to better address the nitrogen needs of the crop during the season and reduce potential water pollution due to nitrates. Considering the amount of synthetic nitrogen fertilizer saved by using both organic soil amendment and green manuring, there should be fewer potential carbon emissions due to the production, transportation and field application of synthetic nitrogen fertilizers. [ABSTRACT FROM AUTHOR]