An understanding of the complex contributions of several factors to an urban heat island is crucial for the assessment of the impacts of planning on the thermal conditions within cities. This paper investigates the effects of various factors on the land surface temperature (LST) in three zones of Prague, the capital of the Czech Republic. The investigated factors include the normalized difference vegetation index (NDVI), proximity to lakes larger than 1000 m2 (Lakes), proximity to the river (River), building coverage (BC), and building height (BH). Their interrelationships are explored in a square grid of 30 × 30 m using Landsat-8 data on LST measurements and multiple regression models. The results imply that NDVI significantly reduces LST, followed by the River if within 200 m of it, while the effect of Lakes is negligible. The effect of BH is generally low, though it often also reduces the LST in the outer compact city. BC is a predominant factor in the city, generating a warming effect, which increases with the city’s compactness. The main planning implications are to base urban heat island mitigation strategies on compensating for building coverage with live and dense green bodies in the compact city, promoting vertical development.