Drought and heat-tolerant crops, such as Pearl millet (Pennisetum glaucum), are priority crops for fighting hunger in semi-arid regions. Assessing its performance under future climate scenarios is critical for determining its resilience and sustainability. Field experiments were conducted over two consecutive seasons (2015/2016 and 2016/2017) to determine the yield responses of the crop (pearl millet variety “Okoa”) to microdose fertilizer application in a semi-arid region of Tanzania. Data from the experiment were used to calibrate and validate the DSSAT model (CERES Millet). Subsequently, the model evaluated synthetic climate change scenarios for temperature increments and precipitation changes based on historic observations (2010–2018). Temperature increases of +0.5 to +3.0 ◦C (from baseline), under non-fertilized (NF) and fertilizer microdose (MD) conditions were used to evaluate nine planting dates of pearl millet from early (5 December) to late planting (25 February), based on increments of 10 days. The planting date with the highest yields was subjected to 49 synthetic scenarios of climate change for temperature increments and precipitation changes (of −30% up to +30% from baseline) to simulate yield responses. Results show that the model reproduced the phenology and yield, indicating a very good performance. Model simulations indicate that temperature increases negatively affected yields for all planting dates under NF and MD. Early and late planting windows were more negatively affected than the normal planting window, implying that temperature increases reduced the length of effective planting window for achieving high yields in both NF and MD. Farmers must adjust their planting timing, while the timely availability of seeds and fertilizer is critical. Precipitation increases had a positive effect on yields under all tested temperature increments, but Okoa cultivar only has steady yield increases up to a maximum of 1.5 ◦C, beyond which yields decline. This informs the need for further breeding or testing of other cultivars that are more heat tolerant. However, under MD, the temperature increments and precipitation change scenarios are higher than under NF, indicating a high potential of yield improvement under MD, especially with precipitation increases. Further investigation should focus on other cropping strategies such as the use of in-field rainwater harvesting and heat-tolerant cultivars to mitigate the effects of temperature increase and change in precipitation on pearl millet yield.