Adolescence is a pivotal developmental stage characterised by significant neurobiological changes that heighten susceptibility to substance abuse. This period is marked by the maturation of the brain regions responsible for decision-making and impulse control, alongside an increased sensitivity to rewards driven by dopaminergic pathways. This review aimed to understand adolescent susceptibility to substance abuse using a neuroscientific approach. In line with best practices, data were collected from a variety reliable source to ensure a comprehensive view of the topic. Research studies on adolescent neurodevelopment have contributed to a broader understanding of the physiological and psychological factors at play during adolescence, while grey literature, including expert interviews and focused group discussions, has offered practical insights from frontline professionals, such as psychologists, social workers, and healthcare providers, who deal directly with adolescent substance use. These results demonstrate that the relationship between genetic factors and environmental conditions, such as stress and trauma, intensifies this vulnerability, thereby heightening the likelihood of individuals participating in risky behaviours. This review examines the neuroscientific foundations of substance use during adolescence, highlighting the critical role of timely interventions that utilize neuroplasticity to enhance resilience and reduce risk. By integrating cognitive training and behavioural therapies into public health initiatives, adolescents' cognitive control mechanisms and their propensity for substance abuse can be reduced.