Cotton plays a crucial role in shaping Indian economy and rural livelihoods. The cotton crop is prone to numerous insect pests, necessitating insecticidal application, which increases production costs. The advent of the expression of Bacillus thuringiensis (Bt) insecticidal protein in cotton has significantly reduced the burden of pest without compromising environmental or human health. After the introduction of transgenic cotton, the cultivated area expanded to 22 million hectares, with a 64% increase in adoption by farmers worldwide. Currently, Bt cotton accounts for 93% of the cultivated cotton area in India. However, extensive use of Bt cotton has accelerated resistance development in pests like the pink bollworm. Furthermore, the overreliance on Bt cotton has reduced the use of broad-spectrum pesticides, favouring the emergence of secondary pests with significant challenges. This emphasizes the urgent necessity for developing novel pest management strategies. The high-dose and refuge strategy was initially effective for managing pest resistance in Bt cotton, but its implementation in India faced challenges due to misunderstandings about the use of non-Bt refuge crops. Although gene pyramiding was introduced as a solution, combining mono toxin also led to instances of cross-resistance. Therefore, there is a need for further exploration of biotechnological approaches to manage insect resistance in Bt cotton. Advanced biotechnological strategies, such as sterile insect release, RNA interference (RNAi)-mediated gene silencing, stacking Bt with RNAi, and genome editing using clustered regularly interspaced short palindromic repeats/CRISPR-associated protein (CRISPR-Cas), offer promising tools for identifying and managing resistance genes in insects. Additionally, CRISPR-mediated gene drives and the development of novel biopesticides present potential avenues for effective pest management in cotton cultivation. These innovative approaches could significantly enhance the sustainability and efficacy of pest resistance management in Bt cotton.