Gossypium hirsutum L. (upland cotton) is a crucial fiber crop worldwide, yet the whitefly, Bemisia tabaci Genn, significantly jeopardizes its production. This phloem-feeding pest causes direct damage to the plant and transmits destructive viral diseases. Sustainable cotton production depends on developing whitefly-resistant varieties exhibiting high yield potential. Fortunately, recent progress in molecular biology and genomics offers promising avenues by enabling the identification of key genetic loci and molecular markers associated with both resistance and yield. Whitefly resistance is crucial for cotton production and a comprehensive understanding of its molecular basis remains essential. This review synthesizes current knowledge on the molecular mechanisms of whitefly resistance in cotton, highlighting key genomic regions and candidate genes linked to both resistance and yield. Finally, it explores the potential of marker-assisted selection and genome editing for developing improved cultivars.