Exoskeletons, wearable robotic devices designed to enhance human strength and endurance, find applications in various fields such as healthcare and industry; however, stringent safety measures should be adopted in such settings. This paper presents a comprehensive exploration of challenges associated with exoskeleton technology, ranging from mechanical issues to regulatory and ethical considerations. The enumerated challenges include joint hyper-extension or flexion, rapid or sudden motion, misalignment, fit, and comfort issues, mechanical failure, weight and mobility limitations, environmental challenges, power supply issues, high energy consumption and regeneration, fall risk or stability concerns, sensor failures, control algorithm malfunctions, machine-learning model challenges, communication disconnection, actuator malfunctions, unexpected human-robot interactions, and regulatory and ethical considerations. The paper outlines possible risks and suggests practical solutions based on design, control, and testing methods for each challenge. The objective is to offer a guideline for developers and users, emphasizing safety, reliability, and optimal performance in the ever-evolving landscape of exoskeleton technology. The guideline covers pre-operation checks, user training, emergency response, real-time monitoring, and user interaction to ensure responsible innovation and user-centricity in exoskeleton development and deployment.