This study aimed to determine the optimal plant density, fertiliser rate, number and timing of fertiliser applications for the Burley CSC tobacco cultivar in Dak Lak Province, Vietnam, to ensure high yield and desirable leaf quality. During the 2025–2026 growing season, the plant density and fertiliser rate experiment was arranged in a split-plot design with three plant densities (27,500, 31,000, and 34,500 plants ha⁻¹) and three fertiliser rates (190, 220, and 250 kg N ha⁻¹), with constant rates of 110 kg P₂O₅ and 300 kg K₂O ha⁻¹ and three replications. A randomised complete block design was used to evaluate four fertiliser application regimes at 220:110:300 kg N₂O₅₂O ha⁻¹: two applications at 8 and 25 days after transplanting (DAT), and three applications at 8, 25 and 40; 8, 25 and 45; or 8, 25 and 55 DAT. Plant density, fertiliser rate, and application regime significantly affected growth, yield, and quality. The combination of 34,500 plants ha⁻¹ and 220:110:300 kg N₂O₅₂O ha⁻¹ produced a yield of 3.54 t ha⁻¹, 83.8% grade 1+2 leaves, nicotine content of 4.02%, and a total sensory smoking score of 36.9 points, classified as Good. Increasing N to 250 kg ha⁻¹ did not significantly increase yield but increased bacterial wilt incidence and nicotine content, adversely affecting smoking quality. Among application regimes, three applications at 8, 25 and 45 DAT were most suitable, producing 3.61 t ha⁻¹, 84.9% grade 1+2 leaves, and a sensory smoking score of 36.7 points. Based on these findings, a preliminary optimised agronomic practice is proposed for the Burley CSC cultivar in Dak Lak Province: 34,500 plants ha⁻¹, 220:110:300 kg N₂O₅₂O ha⁻¹, and three fertiliser applications at 8, 25 and 45 DAT. Further studies over one to two growing seasons are required to confirm the stability and consistency of this practice.