This book tries to emphasize the mechanisms associated with the resistance towards various anti-cancer therapies The focus has been given to the role of cancer stem cells, immune cells, and the multiway impact of tumor microenvironment in drug resistance. The book delves into the role of epigenetic alterations, autophagy, intracellular compartments, and the impact of gut microbiome on therapeutic resistance. Each chapter of the book has elaborated on these aspects that are exclusively or mutually driving the therapeutic non-responsiveness towards various current clinical candidates. In addition to that the book has also discussed novel strategies to overcome the therapeutic challenge by employing Combinatorial therapies that can prove to be useful and effective. Overall the book reflects on the current treatment challenges, futuristic strategies and new research initiatives that explore novel treatment options.