Metastatic castration-resistant prostate cancer (mCRPC) has seen significant advancements in treatment and symptom management over the past decade. The management of mCRPC now includes a range of therapeutic options, including chemotherapy, androgen receptor signalling inhibitors (ARSIs), and targeted molecular therapies. The goal of treatment is not only to improve survival but also to enhance quality of life (QoL) and alleviate cancer-related symptoms such as pain. Treatment decisions are influenced by factors including side effects, disease burden, treatment history, comorbidities, patient preference, and the presence of actionable genomic alterations or biomarkers. Docetaxel is the first-line treatment for chemotherapy-naïve patients with good performance status. Novel hormonal agents (NHAs), such as abiraterone and enzalutamide, are effective second-line treatments. These medications can be considered upfront in frail patients or those who are NHA naïve. Genetic testing for mutations in DNA repair deficiency genes is recommended to inform treatment decisions, similar to breast cancer gene testing. Other potential biomarkers being investigated include phosphatase and tensin homologue (PTEN) and homologous recombination repair genes. Despite advances in therapeutic options, mCRPC remains incurable. The advent of novel noncytotoxic agents has enhanced targeted drug delivery and improved treatment responses with favorable toxicity profiles. Trials should continue to incorporate and report health-related QoL scores and functional assessments into their trial designs. PARP inhibitors have shown efficacy in patients with homologous recombination repair (HRR) deficiencies. The PROFOUND study demonstrated that olaparib improved survival in patients with BRCA1/2 mutations. The combination of PARP inhibitors and ARSIs has shown promising results in improving progression-free survival (PFS) and overall survival (OS). The PROpel study demonstrated that the combination of abiraterone and olaparib improved rPFS and OS in mCRPC patients. The PTEN/AKT pathway is also being explored as a potential therapeutic target. Capivasertib and ipatasertib are selective AKT inhibitors that have shown promise in clinical trials. However, challenges remain in targeting AKT isomers and optimizing study designs. Immunotherapy has shown limited success in advanced prostate cancer, with PD-L1 expression not consistently predictive of response. Theranostics, including lutetium-177 PSMA therapy, have shown promise in improving survival and QoL in mCRPC patients. The VISION trial demonstrated that lutetium-177 PSMA-617 improved rPFS and OS in patients with PSMA-positive disease. Overall, the management of mCRPC is evolving with a focus on personalized treatment strategies based on genomic profiling and biomarker-guided approaches. Future research should continue to explore these strategies to improve outcomes and quality of life for patients with mCRPC.Metastatic castration-resistant prostate cancer (mCRPC) has seen significant advancements in treatment and symptom management over the past decade. The management of mCRPC now includes a range of therapeutic options, including chemotherapy, androgen receptor signalling inhibitors (ARSIs), and targeted molecular therapies. The goal of treatment is not only to improve survival but also to enhance quality of life (QoL) and alleviate cancer-related symptoms such as pain. Treatment decisions are influenced by factors including side effects, disease burden, treatment history, comorbidities, patient preference, and the presence of actionable genomic alterations or biomarkers. Docetaxel is the first-line treatment for chemotherapy-naïve patients with good performance status. Novel hormonal agents (NHAs), such as abiraterone and enzalutamide, are effective second-line treatments. These medications can be considered upfront in frail patients or those who are NHA naïve. Genetic testing for mutations in DNA repair deficiency genes is recommended to inform treatment decisions, similar to breast cancer gene testing. Other potential biomarkers being investigated include phosphatase and tensin homologue (PTEN) and homologous recombination repair genes. Despite advances in therapeutic options, mCRPC remains incurable. The advent of novel noncytotoxic agents has enhanced targeted drug delivery and improved treatment responses with favorable toxicity profiles. Trials should continue to incorporate and report health-related QoL scores and functional assessments into their trial designs. PARP inhibitors have shown efficacy in patients with homologous recombination repair (HRR) deficiencies. The PROFOUND study demonstrated that olaparib improved survival in patients with BRCA1/2 mutations. The combination of PARP inhibitors and ARSIs has shown promising results in improving progression-free survival (PFS) and overall survival (OS). The PROpel study demonstrated that the combination of abiraterone and olaparib improved rPFS and OS in mCRPC patients. The PTEN/AKT pathway is also being explored as a potential therapeutic target. Capivasertib and ipatasertib are selective AKT inhibitors that have shown promise in clinical trials. However, challenges remain in targeting AKT isomers and optimizing study designs. Immunotherapy has shown limited success in advanced prostate cancer, with PD-L1 expression not consistently predictive of response. Theranostics, including lutetium-177 PSMA therapy, have shown promise in improving survival and QoL in mCRPC patients. The VISION trial demonstrated that lutetium-177 PSMA-617 improved rPFS and OS in patients with PSMA-positive disease. Overall, the management of mCRPC is evolving with a focus on personalized treatment strategies based on genomic profiling and biomarker-guided approaches. Future research should continue to explore these strategies to improve outcomes and quality of life for patients with mCRPC.