More frequent and intense exposure to extreme heat conditions poses a serious threat to public health. However, evidence on the association between heat and specific diagnoses of morbidity is still limited. We aimed to comprehensively assess the short-term association between cause-specific hospital admissions and high temperature, including the added effect of temperature variability and heat waves and the effect modification by humidity and air pollution. We used data on cause-specific hospital admissions, weather (i.e., temperature and relative humidity), and air pollution [i.e., fine particulate matter with aerodynamic diameter (), fine particulate matter with aerodynamic diameter (), , and ozone ()] for 48 provinces in mainland Spain and the Balearic Islands between 1 January 2006 and 31 December 2019. The statistical analysis was performed for the summer season (June-September) and consisted of two steps. We first applied quasi-Poisson generalized linear regression models in combination with distributed lag nonlinear models (DLNM) to estimate province-specific temperature-morbidity associations, which were then pooled through multilevel univariate/multivariate random-effect meta-analysis. High temperature had a generalized impact on cause-specific hospitalizations, while the added effect of temperature variability [i.e., diurnal temperature range (DTR)] and heat waves was limited to a reduced number of diagnoses. The strongest impact of heat was observed for metabolic disorders and obesity [relative risk (RR) = 1.978; 95% empirical confidence interval (eCI): 1.772, 2.208], followed by renal failure (1.777; 95% eCI: 1.629, 1.939), urinary tract infection (1.746; 95% eCI: 1.578, 1.933), sepsis (1.543; 95% eCI: 1.387, 1.718), urolithiasis (1.490; 95% eCI: 1.338, 1.658), and poisoning by drugs and nonmedicinal substances (1.470; 95% eCI: 1.298, 1.665). We also found differences by sex (depending on the diagnosis of hospitalization) and age (very young children and the elderly were more at risk). Humidity played a role in the association of heat with hospitalizations from acute bronchitis and bronchiolitis and diseases of the muscular system and connective tissue, which were higher in dry days. Moreover, heat-related effects were exacerbated on high pollution days for metabolic disorders and obesity () and diabetes (, ). Short-term exposure to heat was found to be associated with new diagnoses (e.g., metabolic diseases and obesity, blood diseases, acute bronchitis and bronchiolitis, muscular and connective tissue diseases, poisoning by drugs and nonmedicinal substances, complications of surgical and medical care, and symptoms, signs, and ill-defined conditions) and previously identified diagnoses of hospital admissions. The characterization of the vulnerability to heat can help improve clinical and public health practices to reduce the health risks posed by a warming planet. https://doi.org/10.1289/EHP13254.