Background: Colorectal cancer is a common malignancy characterised by the abnormal growth of cells in the colon or rectum. Its high occurrence and death rate make it a significant concern for public health. Hormone signalling pathways including estrogen, progestrone and androgen receptors have gained attention in CRC research for their potential impact on tumor development and progression and open possibilities for newer therapeutic approaches. Objective: The objectives of the study are to investigate the role of sex steroid receptors in colorectal cancer, to explore the potential therapeutic opportunities in CRC treatment, and to discuss the implications of sex specificity in study design and interpretation. Method: Multiple cohort studies were dissected to provide valuable insights into the intricate world of sex steroid receptors in CRC. The results of the cohort studies were analysed based on gender, age, clinical stage and anatomical location. Results: The study emphasizes the intricate roles of sex hormones and their receptors in colorectal cancer (CRC) progression, highlighting that ERβ has anti-tumor effects with lower levels linked to colonic tumors in females, while ERα and androgen receptors (AR) promote growth, particularly in postmenopausal women. Progesterone receptors are linked to poorer prognosis, though progesterone treatment inhibits CRC cell proliferation. In malignant tissues, ERα and AR levels increase, while ERβ and progesterone receptors decrease. ER isoforms’ mRNA levels are lower in malignant female cases, while AR expression is higher in males. Additionally, the location of CRC differs by sex, with women more likely to develop proximal colon cancer—associated with reduced ERβ—while men tend to develop distal CRC. This research reveals anuanced modulation of gene transcription in CRC by ERα, ERβ, and GPER, reflecting both tumor-promoting and suppressive effects of these hormones. Limitations: The study highlights that the mechanism by which progesterone reduces colorectal cancer (CRC) progression remains uncertain. Limitations include variability in findings due to differences in cell lines, hormone concentrations, and receptor expression. The study also notes inconsistencies across research on hormone replacement therapy (HRT) and its potential to reduce CRC risk, suggesting a need for standardized methodologies to evaluate the progesterone receptor’s impact on CRC prognosis. Additionally, it acknowledges the complex interplay between cytokines in the tumor microenvironment and estrogen signaling, creating a challenging feedback loop. Future directions: The article examines emerging therapeutic strategies in colorectal cancer (CRC), suggesting that combined activation of Estrogen Receptor Beta (ERβ) and Progesterone Receptor (PGR) could produce anti-cancer effects. It proposes sequential estrogen-progesterone therapy as a promising regimen for early-stage CRC, while simultaneous therapy may benefit advanced cases. Future research should clarify the role of sex hormones in CRC development, advance prognostic markers, and explore selective estrogen receptor modulators (SERMs) as potential therapies. It also calls for investigation into pharmacological agents targeting ERβ and the influence of the gut microbiome in CRC prevention, paving the way for tailored therapeutic interventions.