This review examines how biotechnology advances (CRISPR/Cas9, next-generation targeted therapies, nanotechnology-based drug delivery, and immunotherapies) can be applied to address cancer drug resistance worldwide. It also considers the economic burden of resistance, inequities in access to biotechnology solutions, and ethical concerns surrounding rapid innovation, particularly in low-resource settings. A narrative review synthesized evidence from basic science studies, clinical trials, translational research, and policy analyses. Evidence was prioritized for 2015–2025 publications. The synthesis highlights resistance biology and evaluates how precision medicine, biomarker-guided treatment, and high-throughput drug screening can inform individualized regimens and rational combinations. Breakthroughs in gene editing, targeted inhibitors, nanocarriers, and immune engineering can counter key resistance mechanisms, including resistance-conferring mutations, altered drug transport, immune evasion, and tumor microenvironment–mediated protection. Despite progress, implementation barriers remain substantial: high drug and development costs, limited molecular diagnostics and manufacturing capacity, and regulatory and governance challenges that can delay adoption and widen disparities, particularly in low- and middle-income countries. Integrating biotechnology innovations within precision medicine frameworks may improve treatment selection and patient outcomes. Maximizing public health impact requires affordability and financing strategies, robust ethical oversight, timely regulatory pathways, and coordinated global collaboration to ensure access to effective therapies across health systems worldwide.