Bladder cancer is a heterogeneous disease, with treatment decisions primarily based on disease stage (non-muscle invasive or muscle-invasive). For non-muscle invasive bladder cancer (NMIBC), transurethral resection of bladder tumor (TURBT) followed by intravesical therapies is the standard approach. Bacillus Calmette–Guerin (BCG) is the primary intravesical therapy, inducing an inflammatory response to recruit immune cells and induce immune memory. However, some patients develop BCG-unresponsive disease, necessitating alternative treatments such as systemic pembrolizumab and Nadofaragene-Firadenovac. Recent logistic issues with BCG production have led to a global shortage, prompting interest in alternative therapies like mitomycin C, sequential gemcitabine with docetaxel, and others. This review covers the historical and current role of BCG in NMIBC treatment, revisits BCG alternative therapies, and reviews novel therapeutics approved for BCG-unresponsive stage or under active investigation. Key points include the efficacy and safety of gemcitabine monotherapy and sequential gemcitabine/docetaxel, the use of mitomycin C, and the potential of thermo-chemotherapy and novel immunotherapies like ALT-803 and oncolytic viral delivery systems. The review highlights the need for further research to standardize protocols and compare therapies, emphasizing the importance of reliable biomarkers to detect progression in NMIBC.Bladder cancer is a heterogeneous disease, with treatment decisions primarily based on disease stage (non-muscle invasive or muscle-invasive). For non-muscle invasive bladder cancer (NMIBC), transurethral resection of bladder tumor (TURBT) followed by intravesical therapies is the standard approach. Bacillus Calmette–Guerin (BCG) is the primary intravesical therapy, inducing an inflammatory response to recruit immune cells and induce immune memory. However, some patients develop BCG-unresponsive disease, necessitating alternative treatments such as systemic pembrolizumab and Nadofaragene-Firadenovac. Recent logistic issues with BCG production have led to a global shortage, prompting interest in alternative therapies like mitomycin C, sequential gemcitabine with docetaxel, and others. This review covers the historical and current role of BCG in NMIBC treatment, revisits BCG alternative therapies, and reviews novel therapeutics approved for BCG-unresponsive stage or under active investigation. Key points include the efficacy and safety of gemcitabine monotherapy and sequential gemcitabine/docetaxel, the use of mitomycin C, and the potential of thermo-chemotherapy and novel immunotherapies like ALT-803 and oncolytic viral delivery systems. The review highlights the need for further research to standardize protocols and compare therapies, emphasizing the importance of reliable biomarkers to detect progression in NMIBC.