Soil fertility depletion and the unavailability of nutrients due to a decline in soil organic matter content and improper fertilizer application are limiting bread wheat productivity in Ethiopia. Hence, a field experiment was conducted in 2023 to determine the effects of integrated use of vermicompost and inorganic fertilizer (NPS and urea) on soil physicochemical properties, yield, and yield components of bread wheat in the Vertisol of Mekaneselam District, North-East Ethiopia. A factorial combination of four levels of vermicompost (0, 3, 6, and 9 t ha-1) and three levels of inorganic fertilizer (NPS and urea) (0%, 50%, and 100% kg ha-1) from the blanket recommendation of 120 kg ha-1 of NPS and 100 kg ha-1 of Urea fertilizers for wheat growing in the study area. The experiment was laid out in a randomized complete block design with three replications. All collected soil data, yield, and yield components of bread wheat data were analyzed using SAS software. After the bread wheat harvest, the soil analysis of variance showed that the soil bulk density (BD), moisture content (MC), soil pH (pH), soil organic carbon (SOC), total nitrogen (TN), available phosphorus (Av.P), cation exchange capacity (CEC), and exchangeable calcium (Ex.Ca) were significantly (p<0.05) affected by the combined application of vermicompost and inorganic fertilize (NPS and urea). The highest MC (46%), pH (6.77), Av.P (19.26 ppm), TN (0.27%), CEC (29.77 cmolc kg-1), and SOC (2.84%) were obtained from the application of 6 and 9 t ha-1 vermicompost with 100% ha-1 of inorganic fertilizer and 9 t ha-1 vermicompost with 50% (combined fertilizer of NPS and urea). However, the lowest MC (40.67%), pH (5.87), Av.P (10.57 ppm), TN (0.18%), CEC (21.00 Cmolc kg-1), and SOC (1.68%) were obtained from the control plot (0% inorganic fertilize (NPS and urea) with 0 t ha-1 vermicompost). The results of bread wheat analysis showed that the grain yield, thousand-grain weight, number of seeds per spike, number of effective tillers, and harvest index were significantly (p<0.05) affected by the combined application of vermicompost and inorganic fertilize (NPS and urea). The maximum bread wheat grain yield (4066.67 kg ha-1), thousand-grain weight (52.67 g), number of seeds per spike (49.8), number of effective tillers (426.35 m2), and harvest index (40.43%) were obtained from the use of 6 t ha-1 vermicompost with 50% ha-1 of inorganic fertilize (NPS and urea). However, the minimum grain yield (1900 kg ha-1), thousand seed weight (42g), number of seeds per spike (30.33), number of effective tillers (292.67 m2), and harvest index (26.4%) were obtained from the control plot (0% inorganic fertilize (NPS and urea) with 0 t ha-1 vermicompost). Moreover, the combined application of 6 t ha-1 vermicompost with 50% inorganic fertilize (NPS and urea) produced the highest bread wheat grain yield and maximum net benefit with a marginal rate of return (965.75%), while the sole application of 50% inorganic fertilizes (NPS and urea) provided the highest marginal rate of return (1241.66%). Thus, it can be concluded that the combined applications of 6 t ha-1 vermicompost and 50% ha-1 of inorganic fertilize (NPS and urea) were the most recommended and economically feasible for bread wheat production and soil fertility improvements in the Vertisol of the study area.