Crop yield and profitability in the dryland production systems of southern Australia are directly affected by the application of nitrogen (N) and phosphorus (P) fertilisers. How efficiently a crop utilises applied fertiliser is affected by several factors that interact in a complex way, including: nutrient mobility, soil type and soil physicochemical and biological factors, season (including rainfall amount and distribution), and crop physiology. In addition, nutrient supply and crop demand need to synchronise both temporally and spatially if nutrient use efficiency is to be optimised. In this study, the mechanistic simulation model, ROOTMAP, was used to investigate and generate hypotheses about the implications of a range of fertiliser management strategies on the nutrient utilisation of wheat. A range of seasons and 2 commercially important soil types (a Wimmera Vertosol and a Mallee Sodosol) were considered. Simulation results showed a strong interaction between the timing and placement of N and P fertiliser, soil type, seasonal conditions, root growth, and nutrient uptake by wheat. This suggests that region-specific recommendations for fertiliser management may be superior to the ‘one size fits all’ approach typically adopted over the Wimmera/Mallee region. Fertiliser use efficiency differed between the 2 soil types, primarily because physicochemical subsoil constraints were present in the Sodosol, but not the Vertosol. These affected rooting depth, total root system size, and root distribution—notably root growth and hence foraging in the topsoil layer. The root growth response to fertiliser management strategies and seasonal rainfall was also reduced on the Sodosol compared with the Vertosol. Simulated fertiliser uptake was responsive to the placement strategy in a dry year characterised by small rainfall events, typical for the Wimmera and Mallee regions. Shallow placement (0.05 or 0.025 m) of N and P in the topsoil utilised topsoil moisture from these small rainfall events, improving crop N and P uptake. The degree of benefit differed between the 2 soil types, and placement of fertiliser was more effective than topdressing. The simulation approach used here provides a preliminary assessment of a range of fertiliser strategies for different soil type and seasonal conditions. However, because ROOTMAP does not provide direct predictions of grain yield response, simulation results need subsequent validation under field conditions before they can be used by growers.