First, recognize that change is constant. You may have escaped losing your job in a downsizing, but now you work overtime to compensate for all those bodies that are no longer there. You may have relied on your college degree to get you to retirement, but now you realize your skills need a major overhaul. You may even be thinking about switching careers to find work you love. If you're in a job that doesn't fit your values, temperament and skills, it will be an uphill battle.
Most people also have to feel that what they do makes some difference in the world.
Sometimes the problem is not that you're unsuited to the work, but that you're in a company culture that does not fit your style or values. In that case, your task is to find the culture that fits you. Throughout your career, you must continually ask yourself these questions, because the answers sometimes change as you mature. Eventually, you'll find a job you love. Behave like an entrepreneur.