Next-generation ground- and space-based infrared telescopes will be capable of measuring the atmospheric compositions of smaller and cooler planets than previous-workhorses Spitzer or Hubble. It is critical that we understand the limitations of these new and upcoming instruments prior to making observations in order to maximize the science returns from low-signal sources without taking years to refine observing strategies and analysis techniques. We use modified versions of ExoSim to model planned and proposed ground- and space-based instruments with high detail, including various realistic systematics and noise sources. These simulations will inform upcoming observing strategies, and new simulations can be readily applied to additional observatories. Additionally, this work enables end-to-end testing of exoplanet data-analysis pipelines, including signal extraction and systematics mitigation. This project was supported by NASA Exoplanets Research Program grant NNX17AB62G.