The live attenuated Mycobacterium bovis strain Bacillus Calmette Guerin (BCG), despite its incomplete and variable efficacy, remains the only licensed Tuberculosis (TB) vaccine, as no vaccine candidate have surpassed BCG efficacy in clinical settings to date. Consequently, TB remains the first cause of death by an infectious disease worldwide despite high-coverage of neonatal BCG vaccination programmes in TB-endemic areas. The World Health Organisation alerted on the urge of the situation and the critical role of effective vaccination strategies to achieve rapid reduction in TB incidence and mortality in near future. Viral vector and mRNA vaccines have recently gained interest since the COVID-19 pandemics, as both these platforms were used to develop safe, efficient vaccines in a record of time. It initiated a new era in vaccine development, representing a new hope for diseases for which conventional vaccine technologies failed to provide sufficient protection. Viral vector and RNA vaccine candidates currently evaluated for prevention of M. tuberculosis infection and TB disease are essentially designed to boost protection induced by prime BCG vaccination. In this chapter, we present an exhaustive historical review of clinical trials assessing safety, immunogenicity and efficacy of viral vector and mRNA candidate vaccines for prevention of Mtb infection and TB disease. Finally, we discuss the successes and failures of these vaccines, the current challenges, and implications for future TB vaccine development.