Cotton (Gossypium hirsutum L.) is an important crop in the United States that is grown across the country stretching from California in the west to Virginia in the east. Increasing production costs, volatile market prices, and shifting mill demand from domestic to overseas markets has resulted in more uncertainty in the cotton market, raising the importance of cotton quality with respect to overall profitability. The Texas High Plains (THP) region has historically grown lower yielding and grade cotton that has utilized stripper harvesting methods. Advances in genetics, crop management, and irrigation efficiency have improved the yield and quality of cotton grown in the region. The objectives of this research were to increase profitability through the most profitable combination of cultivar selection, irrigation and nitrogen level, and harvesting method at the farm level. Specific objectives were to determine if it is more profitable to adopt a picker harvesting system over the currently used stripper harvesting system, whether an increased irrigation and nitrogen level had an impact on overall profitability, and if choosing a picker type cultivar over a stripper type cultivar would increase profitability. Yield, average cotton price, and gross margin were estimated for cultivar selection, irrigation level, nitrogen level, and harvesting system. The results from this study show that producers can increase their gross margin with higher irrigation levels and proper cultivar selection, but do not benefit from increased nitrogen levels. Under the conditions of this study, producers in the THP will not necessarily benefit from switching to a picker harvesting system over the traditional stripper harvesting system. This study highlights the importance for producers to effectively manage inputs and their corresponding levels for overall profitability.